3,615 results
Search Results
2. The people behind the papers - Akane Hatsuda and Mineko Kengaku.
- Subjects
- Humans, Hippocampus metabolism, Neurons metabolism, AMP-Activated Protein Kinases metabolism
- Abstract
Calcium signals evoked by neuronal activity play an important role in dendritic development and establishment of neuronal circuit connectivity. A new study demonstrates a link between activity-dependent dendritic development and AMP-activated protein kinase (AMPK)-dependent mitochondrial homeostasis in rodent hippocampus. We caught up with first author Akane Hatsuda and corresponding author Mineko Kengaku, Professor at Kyoto University., (© 2023. Published by The Company of Biologists Ltd.)
- Published
- 2023
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3. The people behind the papers - Matt Matrongolo and Max Tischfield.
- Subjects
- Humans, Animals, Mice, Research Personnel, Mammals, Neurogenesis, Neurons
- Abstract
Cortical folding is a highly regulated process involving amplification of neuroprogenitor cells, increased neurogenesis and migration of neurons along the tangential axis. A new paper in Development investigates the signalling processes behind cortical folding in mice, which have a smooth brain surface (lissencephaly) that evolved from the loss of folding present in gyrencephalic (folded cortex) mammals. To hear more about the story behind the paper, we caught up with the first author Matt Matrongolo and his supervisor Max Tischfield, Assistant Professor at Rutgers, The State University of New Jersey., (© 2023. Published by The Company of Biologists Ltd.)
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- 2023
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4. The people behind the papers - Carla Argañaraz, Tamara Adjimann and Mariano Soiza-Reilly.
- Subjects
- Humans, Serotonin, Neurons
- Abstract
Serotonin neurons have been implicated in maladaptive neural mechanisms that could contribute to mental disorders such as depression and anxiety. In a new paper in Development, Mariano Soiza-Reilly and colleagues identify a key postnatal period when the synaptic inputs to serotonin neurons undergo profound refinement. We caught up with PhD students and co-first authors Carla Argañaraz and Tamara Adjimann, and corresponding author Mariano Soiza-Reilly, a group leader at the Instituto de Fisiología, Biología Molecular y Neurociencias in Buenos Aires, to find out more about their research., (© 2022. Published by The Company of Biologists Ltd.)
- Published
- 2022
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- View/download PDF
5. Identification of a cold sensor in peripheral somatosensory neurons.
- Subjects
- Cold Temperature, Somatosensory Cortex physiology, Neurons physiology, Interneurons
- Published
- 2024
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- View/download PDF
6. Soft high-density neural probes enable stable single-neuron recordings.
- Subjects
- Microelectrodes, Neurons physiology, Brain physiology
- Published
- 2024
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- View/download PDF
7. DNeuroMAT: A Deep-Learning-Based Neuron Morphology Analysis Toolbox.
- Author
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Liu M, Lin Z, Chen W, Meijering E, and Wang Y
- Subjects
- Software, Animals, Image Processing, Computer-Assisted methods, Brain cytology, Humans, Neurons cytology, Deep Learning, Imaging, Three-Dimensional methods
- Abstract
Digital reconstruction of neuronal structures from 3D neuron microscopy images is critical for the quantitative investigation of brain circuits and functions. Currently, neuron reconstructions are mainly obtained by manual or semiautomatic methods. However, these ways are labor-intensive, especially when handling the huge volume of whole brain microscopy imaging data. Here, we present a deep-learning-based neuron morphology analysis toolbox (DNeuroMAT) for automated analysis of neuron microscopy images, which consists of three modules: neuron segmentation, neuron reconstruction, and neuron critical points detection., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
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8. On the embodied nature of knowledge: From neurons to numbers.
- Author
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Fischer MH
- Subjects
- Humans, Cognition physiology, Knowledge, Neurons physiology
- Abstract
Interdisciplinary investigations of the human mind through the cognitive sciences have identified a key role of the body in representing knowledge. After characterizing knowledge at grounded, embodied, and situated levels, number knowledge is analyzed from this hierarchical perspective. Lateralized cortical processing of coarse versus fine detail is identified as a grounding substrate for the population stereotype few/left, many/right, which then contributes to number-related sensory and motor biases at the embodied and situated levels. Implications of this perspective for education and rehabilitation are discussed., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)
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- 2024
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9. Computational Tools for Neuronal Morphometric Analysis: A Systematic Search and Review.
- Author
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Leite J, Nhoatto F, Jacob A Jr, Santana R, and Lobato F
- Subjects
- Humans, Animals, Brain cytology, Computational Biology methods, Computational Biology trends, Software trends, Image Processing, Computer-Assisted methods, Image Processing, Computer-Assisted trends, Neurons cytology
- Abstract
Morphometry is fundamental for studying and correlating neuronal morphology with brain functions. With increasing computational power, it is possible to extract morphometric characteristics automatically, including features such as length, volume, and number of neuron branches. However, to the best of our knowledge, there is no mapping of morphometric tools yet. In this context, we conducted a systematic search and review to identify and analyze tools within the scope of neuron analysis. Thus, the work followed a well-defined protocol and sought to answer the following research questions: What open-source tools are available for neuronal morphometric analysis? What morphometric characteristics are extracted by these tools? For this, aiming for greater robustness and coverage, the study was based on the paper analysis as well as the study of documentation and tests with the tools available in repositories. We analyzed 1,586 papers and mapped 23 tools, where NeuroM, L-Measure, and NeuroMorphoVis extract the most features. Furthermore, we contribute to the body of knowledge with the unprecedented presentation of 150 unique morphometric features whose terminologies were categorized and standardized. Overall, the study contributes to advancing the understanding of the complex mechanisms underlying the brain., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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10. Dimensionality reduction beyond neural subspaces with slice tensor component analysis.
- Author
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Pellegrino A, Stein H, and Cayco-Gajic NA
- Subjects
- Animals, Mice, Motor Cortex physiology, Models, Neurological, Neurons physiology
- Abstract
Recent work has argued that large-scale neural recordings are often well described by patterns of coactivation across neurons. Yet the view that neural variability is constrained to a fixed, low-dimensional subspace may overlook higher-dimensional structure, including stereotyped neural sequences or slowly evolving latent spaces. Here we argue that task-relevant variability in neural data can also cofluctuate over trials or time, defining distinct 'covariability classes' that may co-occur within the same dataset. To demix these covariability classes, we develop sliceTCA (slice tensor component analysis), a new unsupervised dimensionality reduction method for neural data tensors. In three example datasets, including motor cortical activity during a classic reaching task in primates and recent multiregion recordings in mice, we show that sliceTCA can capture more task-relevant structure in neural data using fewer components than traditional methods. Overall, our theoretical framework extends the classic view of low-dimensional population activity by incorporating additional classes of latent variables capturing higher-dimensional structure., (© 2024. The Author(s).)
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- 2024
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11. Engram mechanisms of memory linking and identity.
- Author
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Choucry A, Nomoto M, and Inokuchi K
- Subjects
- Animals, Humans, Models, Neurological, Synapses physiology, Brain physiology, Memory physiology, Neurons physiology
- Abstract
Memories are thought to be stored in neuronal ensembles referred to as engrams. Studies have suggested that when two memories occur in quick succession, a proportion of their engrams overlap and the memories become linked (in a process known as prospective linking) while maintaining their individual identities. In this Review, we summarize the key principles of memory linking through engram overlap, as revealed by experimental and modelling studies. We describe evidence of the involvement of synaptic memory substrates, spine clustering and non-linear neuronal capacities in prospective linking, and suggest a dynamic somato-synaptic model, in which memories are shared between neurons yet remain separable through distinct dendritic and synaptic allocation patterns. We also bring into focus retrospective linking, in which memories become associated after encoding via offline reactivation, and discuss key temporal and mechanistic differences between prospective and retrospective linking, as well as the potential differences in their cognitive outcomes., (© 2024. Springer Nature Limited.)
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- 2024
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12. Cerebellar granule cell migration and folia development require Mllt11/Af1q/Tcf7c.
- Author
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Blommers M, Stanton-Turcotte D, Witt EA, Heidari M, and Iulianella A
- Subjects
- Pregnancy, Female, Humans, Neuroglia metabolism, Cell Movement physiology, Neurons metabolism, Cerebellum, Embryonic Structures, Metencephalon embryology
- Abstract
The organization of neurons into distinct layers, known as lamination, is a common feature of the nervous system. This process, which arises from the direct coupling of neurogenesis and neuronal migration, plays a crucial role in the development of the cerebellum, a structure exhibiting a distinct folding cytoarchitecture with cells arranged in discrete layers. Disruptions to neuronal migration can lead to various neurodevelopmental disorders, highlighting the significance of understanding the molecular regulation of lamination. We report a role Mllt11/Af1q/Tcf7c (myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 fused gene from chromosome 1q, also known as Mllt11 transcriptional cofactor 7; henceforth referred to Mllt11) in the migration of cerebellar granule cells (GCs). We now show that Mllt11 plays a role in both the tangential and radial migration of GCs. Loss of Mllt11 led to an accumulation of GC precursors in the rhombic lip region and a reduction in the number of GCs successfully populating developing folia. Consequently, this results in smaller folia and an overall reduction in cerebellar size. Furthermore, analysis of the anchoring centers reveals disruptions in the perinatal folia cytoarchitecture, including alterations in the Bergmann glia fiber orientation and reduced infolding of the Purkinje cell plate. Lastly, we demonstrate that Mllt11 interacts with non-muscle myosin IIB (NMIIB) and Mllt11 loss-reduced NMIIB expression. We propose that the dysregulation of NMIIB underlies altered GC migratory behavior. Taken together, the findings reported herein demonstrate a role for Mllt11 in regulating neuronal migration within the developing cerebellum, which is necessary for its proper neuroanatomical organization., (© 2024 The Authors. Developmental Neurobiology published by Wiley Periodicals LLC.)
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- 2024
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13. Recording single-neuron activity during walking in humans.
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- Humans, Walking physiology, Neurons physiology
- Published
- 2023
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14. ACR White Paper on Magnetoencephalography and Magnetic Source Imaging: A Report from the ACR Commission on Neuroradiology
- Author
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J.A. Maldjian, R. Lee, J. Jordan, E.M. Davenport, A.L. Proskovec, M. Wintermark, S. Stufflebeam, J. Anderson, P. Mukherjee, S.S. Nagarajan, P. Ferrari, W. Gaetz, E. Schwartz, and T.P.L. Roberts
- Subjects
Neurons ,Magnetic Phenomena ,Humans ,Magnetoencephalography ,Brain ,Radiology, Nuclear Medicine and imaging ,Neuroimaging ,Neurology (clinical) - Abstract
Magnetoencephalography, the extracranial detection of tiny magnetic fields emanating from intracranial electrical activity of neurons, and its source modeling relation, magnetic source imaging, represent a powerful functional neuroimaging technique, able to detect and localize both spontaneous and evoked activity of the brain in health and disease. Recent years have seen an increased utilization of this technique for both clinical practice and research, in the United States and worldwide. This report summarizes current thinking, presents recommendations for clinical implementation, and offers an outlook for emerging new clinical indications.
- Published
- 2022
15. The people behind the papers - Ingvild Lynneberg Glærum, Keagan Dunville and Giulia Quattrocolo.
- Subjects
- *
COLLEGE teachers , *HIPPOCAMPUS (Brain) , *NEURONS , *THETA rhythm - Abstract
Cajal-Retzius (CR) cells are transient neurons that control cortical lamination during development. Although most CR cells disappear before birth, a small population persists in the hippocampus postnatally for several months. In a new study, Giulia Quattrocolo and colleagues investigate the role of postnatal CR cells in establishing the hippocampal network. To find out more about the story, we caught up with first authors Ingvild Lynneberg Glærum and Keagan Dunville, and corresponding author Giulia Quattrocolo, Associate Professor at Norwegian University of Science and Technology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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16. Transcranial magnetic stimulation of the brain: what is stimulated? - A consensus and critical position paper
- Author
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Hartwig R. Siebner, Klaus Funke, Aman S. Aberra, Andrea Antal, Sven Bestmann, Robert Chen, Joseph Classen, Marco Davare, Vincenzo Di Lazzaro, Peter T. Fox, Mark Hallett, Anke N. Karabanov, Janine Kesselheim, Mikkel M. Beck, Giacomo Koch, David Liebetanz, Sabine Meunier, Carlo Miniussi, Walter Paulus, Angel V. Peterchev, Traian Popa, Michael C. Ridding, Axel Thielscher, Ulf Ziemann, John C. Rothwell, Yoshikazu Ugawa, Siebner, Hartwig R, Funke, Klaus, Aberra, Aman S, Antal, Andrea, Ridding, Michael C, and Ugawa, Yoshikazu
- Subjects
dorsal premotor cortex ,posterior parietal cortex ,i wave interaction ,Consensus ,hz electrical oscillations ,silent period ,Action Potentials ,Mechanism of action ,Motor cortex ,Physiology ,Transcranial magnetic stimulation ,interval intracortical inhibition ,motor cortex ,Physiology (medical) ,transcranial magnetic stimulation ,contralateral primary motor ,Faculty of Science ,Humans ,Neurons ,primary motor cortex ,Brain ,Evoked Potentials, Motor ,Transcranial Magnetic Stimulation ,Sensory Systems ,Neurology ,theta-burst stimulation ,physiology ,frontal-lobe inputs ,Neurology (clinical) ,mechanism of action - Abstract
Copyright © 2022 The Author(s) and International Federation of Clinical Neurophysiology. Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool. Aman S. Aberra was supported by a U. S. A. National Science Foundation Graduate Research Fellowship (No. DGF 1106401). Andrea Antal has been supported by a grant of the Federal Ministry of Education and Research (BMBF) of Germany (Grant 01GP2124B) and by a grant of the Lower Saxony Ministry of Science and Culture (Grant 76251-12-7/19 ZN 3456). Marco Davare has been supported by a BBSRC responsive mode grant. Klaus Funke has been supported by a grant of the Federal Ministry of Education and Research (BMBF) of Germany (Grant 01EE1403B) as part of the German Center for Brain Stimulation (GCBS) and by the Deutsche Forschungsgemeinschaft (DFG) (Grants FU256/3-2; 122679504–SFB874). Mark Hallett is supported by the NINDS Intramural Program. Anke N. Karabanov holds a 4-year Sapere Aude Fellowship which is sponsored by the Independent Research Fund Denmark (Grant Nr. 0169-00027B). The sponsor had no direct involvement in the collection, analysis and interpretation of data and in the writing of the manuscript. Giacomo Koch has been supported by na EU grant H2020-EU.1.2.2. - FET Proactive (Neurotwin ID: 101017716). Sabine Meunier is Emeritus Research Director at INSERM, this has no direct involvement in the collection, analysis and interpretation of data and in the writing of the manuscript. Carlo Miniussi has been supported by a grant of the Caritro Foundation, Italy. Walter Paulus received grants from the Deutsche Forschungsgemeinschaft and BMBF. Angel V. Peterchev was supported by grants from the U. S. A. National Institutes of Health (Grants Nos. R01NS117405, R01NS088674, RF1MH114268, R01MH111865). Traian Popa has been supported by the Defitech Foundation and NIBS-iCog grant from the Swiss National Science Foundation. Hartwig R. Siebner holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant Nr. R186-2015-2138). The salary for Janine Kesselheim (PhD project) has been covered by a project grant “Biophysically adjusted state-informed cortex stimulation” (BASICS) funded by a synergy grant from Novo Nordisk Foundation (PI: Hartwig R Siebner, Interdisciplinary Synergy Program 2014; grant number NNF14OC001). Axel Thielscher has been supported by grants of the Lundbeck foundation (R118-A11308, R244-2017-196 and R313-2019-622). Yoshikazu Ugawa has been supported in part by grants from the Research Project Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (Grants 15H05881, 16H05322, 19H01091, 20K07866). Ulf Ziemann received grants from the German Ministry of Education and Research (BMBF), European Research Council (ERC), and German Research Foundation (DFG).
- Published
- 2022
17. Organizing principles of the prefrontal cortex from a single-neuron projectome.
- Subjects
- Neurons physiology, Prefrontal Cortex physiology
- Published
- 2022
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18. Low-dimensional models of single neurons: a review.
- Author
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Chialva U, González Boscá V, and Rotstein HG
- Subjects
- Action Potentials physiology, Membrane Potentials physiology, Biophysics, Neurons physiology, Models, Neurological
- Abstract
The classical Hodgkin-Huxley (HH) point-neuron model of action potential generation is four-dimensional. It consists of four ordinary differential equations describing the dynamics of the membrane potential and three gating variables associated to a transient sodium and a delayed-rectifier potassium ionic currents. Conductance-based models of HH type are higher-dimensional extensions of the classical HH model. They include a number of supplementary state variables associated with other ionic current types, and are able to describe additional phenomena such as subthreshold oscillations, mixed-mode oscillations (subthreshold oscillations interspersed with spikes), clustering and bursting. In this manuscript we discuss biophysically plausible and phenomenological reduced models that preserve the biophysical and/or dynamic description of models of HH type and the ability to produce complex phenomena, but the number of effective dimensions (state variables) is lower. We describe several representative models. We also describe systematic and heuristic methods of deriving reduced models from models of HH type., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
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19. Regulation of early cerebellar development.
- Author
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Lowenstein ED, Cui K, and Hernandez-Miranda LR
- Subjects
- Animals, Humans, Developmental Biology, GABAergic Neurons cytology, Homeostasis, Neurosciences, Single-Cell Analysis, Cerebellum anatomy & histology, Cerebellum cytology, Cerebellum embryology, Neurons classification, Neurons cytology, Neurons metabolism
- Abstract
The study of cerebellar development has been at the forefront of neuroscience since the pioneering work of Wilhelm His Sr., Santiago Ramón y Cajal and many others since the 19th century. They laid the foundation to identify the circuitry of the cerebellum, already revealing its stereotypic three-layered cortex and discerning several of its neuronal components. Their work was fundamental in the acceptance of the neuron doctrine, which acknowledges the key role of individual neurons in forming the basic units of the nervous system. Increasing evidence shows that the cerebellum performs a variety of homeostatic and higher order neuronal functions beyond the mere control of motor behaviour. Over the last three decades, many studies have revealed the molecular machinery that regulates distinct aspects of cerebellar development, from the establishment of a cerebellar anlage in the posterior brain to the identification of cerebellar neuron diversity at the single cell level. In this review, we focus on summarizing our current knowledge on early cerebellar development with a particular emphasis on the molecular determinants that secure neuron specification and contribute to the diversity of cerebellar neurons., (© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2023
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20. Periods of synchronized myelin changes shape brain function and plasticity.
- Author
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de Faria O Jr, Pivonkova H, Varga B, Timmler S, Evans KA, and Káradóttir RT
- Subjects
- Animals, Brain cytology, Humans, Oligodendroglia physiology, White Matter cytology, Brain physiology, Myelin Sheath physiology, Neuronal Plasticity physiology, Neurons physiology, White Matter physiology
- Abstract
Myelin, a lipid membrane that wraps axons, enabling fast neurotransmission and metabolic support to axons, is conventionally thought of as a static structure that is set early in development. However, recent evidence indicates that in the central nervous system (CNS), myelination is a protracted and plastic process, ongoing throughout adulthood. Importantly, myelin is emerging as a potential modulator of neuronal networks, and evidence from human studies has highlighted myelin as a major player in shaping human behavior and learning. Here we review how myelin changes throughout life and with learning. We discuss potential mechanisms of myelination at different life stages, explore whether myelin plasticity provides the regenerative potential of the CNS white matter, and question whether changes in myelin may underlie neurological disorders., (© 2021. Springer Nature America, Inc.)
- Published
- 2021
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21. Technical approaches and challenges to study AMPA receptors in oligodendrocyte lineage cells: Past, present, and future.
- Author
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Perez-Gianmarco L, Kurt B, and Kukley M
- Subjects
- Cell Lineage, Neuroglia metabolism, Oligodendroglia metabolism, Synapses metabolism, Synaptic Transmission, Receptors, AMPA metabolism, Neurons metabolism
- Abstract
Receptors for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPARs) are ligand-gated ionotropic receptors for glutamate that is a major excitatory neurotransmitter in the central nervous system. AMPARs are located at postsynaptic sites of neuronal synapses where they mediate fast synaptic signaling and synaptic plasticity. Remarkably, AMPARs are also expressed by glial cells. Their expression by the oligodendrocyte (OL) lineage cells is of special interest because AMPARs mediate fast synaptic communication between neurons and oligodendrocyte progenitor cells (OPCs), modulate proliferation and differentiation of OPCs, and may also be involved in regulation of myelination. On the other hand, during pathological conditions, AMPARs may mediate damage of the OL lineage cells. In the present review, we focus on the technical approaches that have been used to study AMPARs in the OL lineage cells, and discuss future perspectives of AMPAR research in these glial cells., (© 2022 Wiley Periodicals LLC.)
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- 2023
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22. A scoping review of mathematical models covering Alzheimer's disease progression.
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Moravveji, Seyedadel, Doyon, Nicolas, Mashreghi, Javad, and Duchesne, Simon
- Subjects
ALZHEIMER'S disease ,MATHEMATICAL models ,DISEASE progression ,TAU proteins ,PARTIAL differential equations - Abstract
Alzheimer's disease is a complex, multi-factorial, and multi-parametric neurodegenerative etiology. Mathematical models can help understand such a complex problem by providing a way to explore and conceptualize principles, merging biological knowledge with experimental data into a model amenable to simulation and external validation, all without the need for extensive clinical trials. We performed a scoping review of mathematical models describing the onset and evolution of Alzheimer's disease as a result of biophysical factors following the PRISMA standard. Our search strategy applied to the PubMed database yielded 846 entries. After using our exclusion criteria, only 17 studies remained from which we extracted data, which focused on three aspects of mathematical modeling: how authors addressed continuous time (since even when the measurements are punctual, the biological processes underlying Alzheimer's disease evolve continuously), howmodels were solved, and how the high dimensionality and non-linearity of models were managed. Most articles modeled Alzheimer's disease at the cellular level, operating on a short time scale (e.g., minutes or hours), i.e., the micro view (12/17); the rest considered regional or brain-level processes with longer timescales (e.g., years or decades) (the macro view). Most papers were concerned primarily with amyloid beta (n = 8), few described both amyloid beta and tau proteins (n = 3), while some considered more than these two factors (n = 6). Models used partial differential equations (n = 3), ordinary differential equations (n = 7), and both partial differential equations and ordinary differential equations (n = 3). Some did not specify their mathematical formalism (n = 4). Sensitivity analyses were performed in only a small number of papers (4/17). Overall, we found that only two studies could be considered valid in terms of parameters and conclusions, and two more were partially valid. This puts the majority (n = 13) as being either invalid or with insufficient information to ascertain their status. This was themain finding of our paper, in that serious shortcomings make their results invalid or non-reproducible. These shortcomings come from insufficient methodological description, poor calibration, or the impossibility of experimentally validating or calibrating the model. Those shortcomings should be addressed by future authors to unlock the usefulness of mathematicalmodels in Alzheimer's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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23. Microglia form satellites with different neuronal subtypes in the adult murine central nervous system.
- Author
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Bakina O, Kettenmann H, and Nolte C
- Subjects
- Animals, Brain, Male, Mice, Microglia physiology, Neurons physiology
- Abstract
Microglia are the innate immune cells of the central nervous system (CNS). In the adult uncompromised CNS, they have a highly ramified morphology and continuously extend and retract their processes. A subpopulation of microglial cells forms close soma-to-soma contacts with neurons and have been termed satellite microglia, yet the role of such interaction is largely unknown. Here, we analyzed the distribution of satellite microglia in different areas of the CNS of adult male mice applying transgenic- and immunolabeling of neuronal subtypes and microglia followed by three-dimensional imaging analysis. We quantified satellite microglia associated with GABAergic and glutamatergic neurons in the somatosensory cortex, striatum, and thalamus; with dopaminergic and serotonergic neurons in the basal forebrain and raphe nucleus, respectively; and with cerebellar Purkinje cell neurons. Satellite microglia in the retina were assessed qualitatively. Microglia form satellites with all neuronal subtypes studied, whereas a preference for a specific neuron subtype was not found. The occurrence and frequency of satellite microglia is determined by the histo-architectural organization of the brain area and the densities of neuronal somata therein., (© 2022 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)
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- 2022
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24. A discrete neuronal population coordinates brain-wide developmental activity.
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Bajar BT, Phi NT, Isaacman-Beck J, Reichl J, Randhawa H, and Akin O
- Subjects
- Animals, Brain physiology, Drosophila, Neurogenesis physiology, Neurons physiology, Synapses physiology
- Abstract
In vertebrates, stimulus-independent activity accompanies neural circuit maturation throughout the developing brain
1,2 . The recent discovery of similar activity in the developing Drosophila central nervous system suggests that developmental activity is fundamental to the assembly of complex brains3 . How such activity is coordinated across disparate brain regions to influence synaptic development at the level of defined cell types is not well understood. Here we show that neurons expressing the cation channel transient receptor potential gamma (Trpγ) relay and pattern developmental activity throughout the Drosophila brain. In trpγ mutants, activity is attenuated globally, and both patterns of activity and synapse structure are altered in a cell-type-specific manner. Less than 2% of the neurons in the brain express Trpγ. These neurons arborize throughout the brain, and silencing or activating them leads to loss or gain of brain-wide activity. Together, these results indicate that this small population of neurons coordinates brain-wide developmental activity. We propose that stereotyped patterns of developmental activity are driven by a discrete, genetically specified network to instruct neural circuit assembly at the level of individual cells and synapses. This work establishes the fly brain as an experimentally tractable system for studying how activity contributes to synapse and circuit formation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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25. Plasticity of microglia.
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Augusto-Oliveira M, Arrifano GP, Delage CI, Tremblay MÈ, Crespo-Lopez ME, and Verkhratsky A
- Subjects
- Central Nervous System, Microglia metabolism, Neurons physiology
- Abstract
Microglial cells are the scions of foetal macrophages which invade the neural tube early during embryogenesis. The nervous tissue environment instigates the phenotypic metamorphosis of foetal macrophages into idiosyncratic surveilling microglia, which are generally characterised by a small cell body and highly ramified motile processes that constantly scan the nervous tissue for signs of changes in homeostasis and allow microglia to perform crucial homeostatic functions. The surveilling microglial phenotype is evolutionarily conserved from early invertebrates to humans. Despite this evolutionary conservation, microglia show substantial heterogeneity in their gene and protein expression, as well as morphological appearance. These differences are age, region and context specific and reflect a high degree of plasticity underlying the life-long adaptation of microglia, supporting the exceptional adaptive capacity of the central nervous system. Microgliocytes are essential elements of cellular network formation and refinement in the developing nervous tissue. Several distinct patrolling modes of microglial processes contribute to the formation, modification, and pruning of synapses; to the support and protection of neurones through microglial-somatic junctions; and to the control of neuronal and axonal excitability by specific microglia-axonal contacts. In pathology, microglia undergo proliferation and reactive remodelling known as microgliosis, which is context dependent, yet represents an evolutionarily conserved defence response. Microgliosis results in the emergence of multiple disease and context-specific reactive states; in addition, neuropathology is associated with the appearance of specific protective or recovery microglial forms. In summary, the plasticity of microglia supports the development and functional activity of healthy nervous tissue and provides highly sophisticated defences against disease., (© 2021 Cambridge Philosophical Society.)
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- 2022
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26. Modeling Dendrites and Spatially-Distributed Neuronal Membrane Properties.
- Author
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Chavlis S and Poirazi P
- Subjects
- Biophysics, Computer Simulation, Synapses physiology, Dendrites physiology, Neurons physiology
- Abstract
The first step toward understanding the brain is to learn how individual neurons process incoming signals, the vast majority of which arrive in their dendrites. Dendrites were first discovered at the beginning of the twentieth century and were characterized by great anatomical variability, both within and across species. Over the past years, a rich repertoire of active and passive dendritic mechanisms has been unveiled, which greatly influences their integrative power. Yet, our understanding of how dendrites compute remains limited, mainly because technological limitations make it difficult to record from dendrites directly and manipulate them. Computational modeling, on the other hand, is perfectly suited for this task. Biophysical models that account for the morphology as well as passive and active neuronal properties can explain a wide variety of experimental findings, shedding new light on how dendrites contribute to neuronal and circuit computations. This chapter aims to help the interested reader build biophysical models incorporating dendrites by detailing how their electrophysiological properties can be described using simple mathematical frameworks. We start by discussing the passive properties of dendrites and then give an overview of how active conductances can be incorporated, leading to realistic in silico replicas of biological neurons., (© 2022. Springer Nature Switzerland AG.)
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- 2022
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27. Developmental timetables and gradients of neurogenesis in cerebellar Purkinje cells and deep glutamatergic neurons: A comparative study between the mouse and the rat.
- Author
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Martí-Clúa J
- Subjects
- Animals, Autoradiography, Female, Mice, Neurogenesis, Pregnancy, Rats, Rats, Inbred Strains, Thymidine, Neurons, Purkinje Cells
- Abstract
The aim of this report is to determine whether the times of neuron origin and neurogenetic gradients of PCs and Deep cerebellar nucli (DCN) glutamatergic neurons are different between mice and rats. Purkinje cells (PCs) were analyzed in each compartment of the cerebellar cortex (vermis, paravermis, medial, and lateral hemispheres), and deep glutamatergic neurons at the level of the medialis, interpositus, and lateralis nuclei. Tritiated thymidine ([
3 H]TdR) autoradiography was applied on sections. The experimental rodents were the offspring of pregnant dams injected with [3 H]TdR on embryonic days (E) 11-12, E12-13, E13-14, E14-15, E15-16, and E16-17. Our results indicate that systematic differences exist in the pattern of neurogenesis and the spatial location of cerebellar PCs and deep glutamatergic neurons between mice and rats. In mice, PCs and deep glutamatergic neurons neurogenesis extend from E10 to E14, with a predominance of neurogenesis on E12 for PCs, and on E12, E11, and E10 for the medialis, interpositus, and lateralis neurons, respectively. When neurogenesis in rats was considered, the data reveal that PCs and deep glutamatergic neurons production extends from E12 to E16, with a peak of production on E14 for PCs, and on E14, E13, and E12 for the medialis, interpositus, and lateralis neurons, respectively. Current data also indicate that, both in mice and rats, both types of macroneurons are generated according to a lateral-to-medial gradient. Thus, the lateral hemisphere and the lateralis nucleus present more early-generated neurons than the vermis and the medialis nucleus, which in their turn have more late-produced neurons., (© 2021 American Association for Anatomy.)- Published
- 2021
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28. Pharmacological preconditioning by TERT inhibitor BIBR1532 confers neuronal ischemic tolerance through TERT-mediated transcriptional reprogramming.
- Author
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Xie X, Li M, Zhou M, Chow SF, and Tsang CK
- Subjects
- Animals, Antioxidants metabolism, Binding Sites genetics, Brain Ischemia pathology, Chromatin metabolism, Chromosome Mapping, Female, Gene Knockdown Techniques, Glucose deficiency, Hypoxia, Ischemic Preconditioning, Mice, Mice, Inbred C57BL, Neuroprotection, Pregnancy, Primary Cell Culture, Reactive Oxygen Species, Signal-To-Noise Ratio, Telomerase antagonists & inhibitors, Telomerase genetics, Transcriptional Activation, Aminobenzoates therapeutic use, Brain Ischemia drug therapy, Naphthalenes therapeutic use, Neurons, Reverse Transcriptase Inhibitors pharmacology, Telomerase metabolism
- Abstract
After a sublethal ischemic preconditioning (IPC) stimulus, the brain has a remarkable capability of acquiring tolerance to subsequent ischemic insult by establishing precautionary self-protective mechanism. Understanding this endogenous mechanism would reveal novel and effective neuroprotective targets for ischemic brain injury. Our previous study has implied that telomerase reverse transcriptase (TERT) is associated with IPC-induced tolerance. Here, we investigated the mechanism of TERT-mediated ischemic tolerance. Preconditioning was modeled by oxygen-glucose deprivation (OGD) and by TERT inhibitor BIBR1532 in primary neurons. We found that ischemic tolerance was conferred by BIBR1532 preconditioning. We used the Cleavage-Under-Targets-And-Tagmentation approach, a recently developed method with superior signal-to-noise ratio, to comprehensively map the genomic binding sites of TERT in primary neurons, and showed that more than 50% of TERT-binding sites were located at the promoter regions. Mechanistically, we demonstrated that under normal conditions TERT physically bound to many previously unknown genomic loci in neurons, whereas BIBR1532 preconditioning significantly altered TERT-chromatin-binding profile. Intriguingly, we found that BIBR1532-preconditioned neurons showed significant up-regulation of promoter binding of TERT to the mitochondrial anti-oxidant genes, which were correlated with their elevated expression. Functional analysis further indicated that BIBR1532-preconditioning significantly reduced ROS levels and enhanced tolerance to severe ischemia-induced mitochondrial oxidative stress in neurons in a TERT-dependent manner. Together, these results demonstrate that BIBR1532 confers neuronal ischemic tolerance through TERT-mediated transcriptional reprogramming for up-regulation of mitochondrial anti-oxidation gene expression, suggesting the translational potential of BIBR1532 as a therapeutic agent for the treatment of cerebral ischemic injury and oxidative stress-induced neurological disorders., (© 2021 International Society for Neurochemistry.)
- Published
- 2021
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29. New perspective on the regulation of acetylcholinesterase via the aryl hydrocarbon receptor.
- Author
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Xie HQ, Ma Y, Fu H, Xu T, Luo Y, Liu Y, Chen Y, Xu L, Xia Y, and Zhao B
- Subjects
- Animals, Brain drug effects, Brain metabolism, Cells, Cultured, Dioxins toxicity, Humans, Neurodegenerative Diseases chemically induced, Neurodegenerative Diseases metabolism, Neurons drug effects, Acetylcholinesterase metabolism, Dioxins metabolism, Neurons metabolism, Receptors, Aryl Hydrocarbon metabolism
- Abstract
Acetylcholinesterase (AChE, EC 3.1.1.7) plays important roles in cholinergic neurotransmission and has been widely recognized as a biomarker for monitoring pollution by organophosphate (OP) and carbamate pesticides. Dioxin is an emerging environmental AChE disruptor and is a typical persistent organic pollutant with multiple toxic effects on the nervous system. Growing evidence has shown that there is a significant link between dioxin exposure and neurodegenerative diseases and neurodevelopmental disorders, most of which involve AChE and cholinergic dysfunctions. Therefore, an in-depth understanding of the effects of dioxin on AChE and the related mechanisms of action might help to shed light on the molecular bases of dioxin impacts on the nervous system. In the past decade, the effects of dioxins on AChE have been revealed in cultured cells of different origins and in rodent animal models. Unlike OP and carbamate pesticides, dioxin-induced AChE disturbance is not due to direct inhibition of enzymatic activity; instead, dioxin causes alterations of AChE expression in certain models. As a widely accepted mechanism for most dioxin effects, the aryl hydrocarbon receptor (AhR)-dependent pathway has become a research focus in studies on the mechanism of action of dioxin-induced AChE dysregulation. In this mini-review, the effects of dioxin on AChE and the diverse roles of the AhR pathway in AChE regulation are summarized. Additionally, the involvement of AhR in AChE regulation during different neurodevelopmental processes is discussed. These AhR-related findings might also provide new insight into AChE regulation triggered by diverse xenobiotics capable of interacting with AhR., (© 2020 International Society for Neurochemistry.)
- Published
- 2021
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30. MAM-2201, One of the Most Potent-Naphthoyl Indole Derivative-Synthetic Cannabinoids, Exerts Toxic Effects on Human Cell-Based Models of Neurons and Astrocytes.
- Author
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Coccini T, De Simone U, Lonati D, Scaravaggi G, Marti M, and Locatelli CA
- Subjects
- Astrocytes pathology, Cell Line, Tumor, Cell Transdifferentiation drug effects, Cell Transdifferentiation physiology, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Neurons pathology, Astrocytes drug effects, Cannabinoids toxicity, Indoles toxicity, Naphthalenes toxicity, Neurons drug effects
- Abstract
Considering the consequences on human health, in general population and workplace, associated with the use of new psychoactive substances and their continuous placing on the market, novel in vitro models for neurotoxicology research, applying human-derived CNS cells, may provide a means to understand the mechanistic basis of molecular and cellular alterations in brain. Cytotoxic effects of MAM-2201, a potent-naphthoyl indole derivative-synthetic cannabinoid, have been evaluated applying a panel of human cell-based models of neurons and astrocytes, testing different concentrations (1-30 µM) and exposure times (3-24-48 h). MAM-2201 induced toxicity in primary neuron-like cells (hNLCs), obtained from transdifferentiation of mesenchymal stem cells derived from human umbilical cord. Effects occurred in a concentration- and time-dependent manner. The lowest concentration affecting cell viability, metabolic function, apoptosis, morphology, and neuronal markers (MAP-2, NSE) was 5 μM, and even 1 μM induced apoptosis. Effects appeared early (3 h) and persisted after 24 and 48 h. Similar behavior was evidenced for human D384-astrocytes treated with MAM-2201. Differently, human SH-SY5Y-neurons, both differentiated and undifferentiated, were not sensitive to MAM-2201. On D384, the different altered endpoints were reversed, attenuated, or not antagonized by AM251 indicating that CB1 receptors may partially mediate MAM-2201-induced cytotoxicity. While in hNLCs, all toxic effects caused by MAM-2201 were apparently unrelated to CB-receptors since they were not evidenced by immunofluorescence. The present in vitro findings demonstrate the cytotoxicity of MAM-2201 on human primary neurons (hNLCs) and astrocytes cell line (D384), and support the use of these cellular models as species-specific in vitro tools suitable to clarify the neurotoxicity mechanisms of synthetic cannabinoids., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2021
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31. Procurement Of Elgi Make Compressor Spares - Elgi Neuron Ii Controller Spel016947
- Subjects
Purchasing ,Neurons ,Paper mills ,Business, international - Abstract
Tenders are invited for Procurement of Elgi Make Compressor Spares - Elgi neuron II controller SPEL016947 Tender Category : Goods Major organization : Security Paper Mill Address : Security Paper [...]
- Published
- 2023
32. Electrocardiography Classification with Leaky Integrate-and-Fire Neurons in an Artificial Neural Network-Inspired Spiking Neural Network Framework.
- Author
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Rana, Amrita and Kim, Kyung Ki
- Subjects
ARTIFICIAL neural networks ,RETINAL blood vessels ,ELECTROCARDIOGRAPHY ,HEART diseases ,NEURONS ,LEARNING strategies - Abstract
Monitoring heart conditions through electrocardiography (ECG) has been the cornerstone of identifying cardiac irregularities. Cardiologists often rely on a detailed analysis of ECG recordings to pinpoint deviations that are indicative of heart anomalies. This traditional method, while effective, demands significant expertise and is susceptible to inaccuracies due to its manual nature. In the realm of computational analysis, Artificial Neural Networks (ANNs) have gained prominence across various domains, which can be attributed to their superior analytical capabilities. Conversely, Spiking Neural Networks (SNNs), which mimic the neural activity of the brain more closely through impulse-based processing, have not seen widespread adoption. The challenge lies primarily in the complexity of their training methodologies. Despite this, SNNs offer a promising avenue for energy-efficient computational models capable of displaying a high-level performance. This paper introduces an innovative approach employing SNNs augmented with an attention mechanism to enhance feature recognition in ECG signals. By leveraging the inherent efficiency of SNNs, coupled with the precision of attention modules, this model aims to refine the analysis of cardiac signals. The novel aspect of our methodology involves adapting the learned parameters from ANNs to SNNs using leaky integrate-and-fire (LIF) neurons. This transfer learning strategy not only capitalizes on the strengths of both neural network models but also addresses the training challenges associated with SNNs. The proposed method is evaluated through extensive experiments on two publicly available benchmark ECG datasets. The results show that our model achieves an overall accuracy of 93.8% on the MIT-BIH Arrhythmia dataset and 85.8% on the 2017 PhysioNet Challenge dataset. This advancement underscores the potential of SNNs in the field of medical diagnostics, offering a path towards more accurate, efficient, and less resource-intensive analyses of heart diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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33. First person - Alexandra Fletcher-Jones.
- Subjects
CANNABINOID receptors ,CYTOLOGY ,NEURONS ,BIOLOGISTS ,RESEARCH personnel - Abstract
This document is an interview with Alexandra Fletcher-Jones, the first author of a paper titled "SGIP1 binding to the α-helical H9 domain of cannabinoid receptor 1 promotes axonal surface expression." The paper explores the role of the endocannabinoid signaling system (ECS) in the brain and how it is regulated. The study found that a protein called SGIP1 binds to cannabinoid receptor 1 (CB1R) to keep it in the correct place, and when SGIP1 is removed, CB1R is less stable and its effects are reduced. Understanding the regulation of CB1R could help in the development of cannabinoid-based drugs for various diseases. The interview also discusses the challenges faced during the project and the author's motivations and future plans in science. [Extracted from the article]
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- 2024
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34. Astrocytes as a mechanism for contextually-guided network dynamics and function.
- Author
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Gong, Lulu, Pasqualetti, Fabio, Papouin, Thomas, and Ching, ShiNung
- Subjects
ASTROCYTES ,REINFORCEMENT learning ,NEURAL circuitry ,SYNAPSES ,CLASSROOM environment ,NEURONS - Abstract
Astrocytes are a ubiquitous and enigmatic type of non-neuronal cell and are found in the brain of all vertebrates. While traditionally viewed as being supportive of neurons, it is increasingly recognized that astrocytes play a more direct and active role in brain function and neural computation. On account of their sensitivity to a host of physiological covariates and ability to modulate neuronal activity and connectivity on slower time scales, astrocytes may be particularly well poised to modulate the dynamics of neural circuits in functionally salient ways. In the current paper, we seek to capture these features via actionable abstractions within computational models of neuron-astrocyte interaction. Specifically, we engage how nested feedback loops of neuron-astrocyte interaction, acting over separated time-scales, may endow astrocytes with the capability to enable learning in context-dependent settings, where fluctuations in task parameters may occur much more slowly than within-task requirements. We pose a general model of neuron-synapse-astrocyte interaction and use formal analysis to characterize how astrocytic modulation may constitute a form of meta-plasticity, altering the ways in which synapses and neurons adapt as a function of time. We then embed this model in a bandit-based reinforcement learning task environment, and show how the presence of time-scale separated astrocytic modulation enables learning over multiple fluctuating contexts. Indeed, these networks learn far more reliably compared to dynamically homogeneous networks and conventional non-network-based bandit algorithms. Our results fuel the notion that neuron-astrocyte interactions in the brain benefit learning over different time-scales and the conveyance of task-relevant contextual information onto circuit dynamics. Author summary: Astrocytes, a non-neuronal cell type, constitute a significant portion of all cells in the brain, yet our understanding of their involvement in neural computation remains limited. In this paper, we use computational modeling to examine how astrocytes may interact with neurons to expand the types of activity and, ultimately, computations that neurons can produce. Two features of astrocytes make them interesting in this context. First, a single astrocyte is able to modulate dozens of neurons and synaptic connections between them. Furthermore, this modulation occurs at slower temporal scales than the neural activity itself, thus meaning that astrocytes could have long-lasting effects on neural activity and connectivity. Our computational models capture both of these features. Using these models, we show that networks with astrocytes can more readily adapt to slowly varying task parameters versus those with neurons alone. We further analyze the models to understand, in mathematical terms, why such effects may arise. Our results shed light on the potential computational role of this common, but enigmatic type of brain cell. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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35. Complete Neuron Reconstruction Based on Branch Confidence.
- Author
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Zeng, Ying and Wang, Yimin
- Subjects
NEURONS ,MARKOV processes ,BRAIN research ,BRAIN diseases ,CONFIDENCE - Abstract
In the past few years, significant advancements in microscopic imaging technology have led to the production of numerous high-resolution images capturing brain neurons at the micrometer scale. The reconstructed structure of neurons from neuronal images can serve as a valuable reference for research in brain diseases and neuroscience. Currently, there lacks an accurate and efficient method for neuron reconstruction. Manual reconstruction remains the primary approach, offering high accuracy but requiring significant time investment. While some automatic reconstruction methods are faster, they often sacrifice accuracy and cannot be directly relied upon. Therefore, the primary goal of this paper is to develop a neuron reconstruction tool that is both efficient and accurate. The tool aids users in reconstructing complete neurons by calculating the confidence of branches during the reconstruction process. The method models the neuron reconstruction as multiple Markov chains, and calculates the confidence of the connections between branches by simulating the reconstruction artifacts in the results. Users iteratively modify low-confidence branches to ensure precise and efficient neuron reconstruction. Experiments on both the publicly accessible BigNeuron dataset and a self-created Whole-Brain dataset demonstrate that the tool achieves high accuracy similar to manual reconstruction, while significantly reducing reconstruction time. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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36. The "psychiatric" neuron: the psychic neuron of the cerebral cortex, revisited.
- Author
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Flynn, L. Taylor, Bouras, Nadia N., Migovich, Volodar M., Clarin, Jacob D., and Wen-Jun Gao
- Subjects
CEREBRAL cortex ,PYRAMIDAL neurons ,SHORT-term memory ,NEURONS ,MEMORY disorders ,PREFRONTAL cortex - Abstract
Nearly 25 years ago, Dr. Patricia Goldman-Rakic published her review paper, "The 'Psychic' Neuron of the Cerebral Cortex," outlining the circuit-level dynamics, neurotransmitter systems, and behavioral correlates of pyramidal neurons in the cerebral cortex, particularly as they relate to working memory. In the decades since the release of this paper, the existing literature and our understanding of the pyramidal neuron have increased tremendously, and research is still underway to better characterize the role of the pyramidal neuron in both healthy and psychiatric disease states. In this review, we revisit Dr. Goldman-Rakic's characterization of the pyramidal neuron, focusing on the pyramidal neurons of the prefrontal cortex (PFC) and their role in working memory. Specifically, we examine the role of PFC pyramidal neurons in the intersection of working memory and social function and describe how deficits in working memory may actually underlie the pathophysiology of social dysfunction in psychiatric disease states. We briefly describe the cortico-cortical and corticothalamic connections between the PFC and non-PFC brain regions, as well the microcircuit dynamics of the pyramidal neuron and interneurons, and the role of both these macroand microcircuits in the maintenance of the excitatory/inhibitory balance of the cerebral cortex for working memory function. Finally, we discuss the consequences to working memory when pyramidal neurons and their circuits are dysfunctional, emphasizing the resulting social deficits in psychiatric disease states with known working memory dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. Neural flip-flops I: Short-term memory.
- Author
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Yoder, Lane
- Subjects
SHORT-term memory ,ACTION potentials ,FLIP-flops (Sandals) ,MEMORY testing ,NEURONS - Abstract
The networks proposed here show how neurons can be connected to form flip-flops, the basic building blocks in sequential logic systems. The novel neural flip-flops (NFFs) are explicit, dynamic, and can generate known phenomena of short-term memory. For each network design, all neurons, connections, and types of synapses are shown explicitly. The neurons' operation depends only on explicitly stated, minimal properties of excitement and inhibition. This operation is dynamic in the sense that the level of neuron activity is the only cellular change, making the NFFs' operation consistent with the speed of most brain functions. Memory tests have shown that certain neurons fire continuously at a high frequency while information is held in short-term memory. These neurons exhibit seven characteristics associated with memory formation, retention, retrieval, termination, and errors. One of the neurons in each of the NFFs produces all of the characteristics. This neuron and a second neighboring neuron together predict eight unknown phenomena. These predictions can be tested by the same methods that led to the discovery of the first seven phenomena. NFFs, together with a decoder from a previous paper, suggest a resolution to the longstanding controversy of whether short-term memory depends on neurons firing persistently or in brief, coordinated bursts. Two novel NFFs are composed of two and four neurons. Their designs follow directly from a standard electronic flip-flop design by moving each negation symbol from one end of the connection to the other. This does not affect the logic of the network, but it changes the logic of each component to a logic function that can be implemented by a single neuron. This transformation is reversible and is apparently new to engineering as well as neuroscience. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. Terahertz Radiation Modulates Neuronal Morphology and Dynamics Properties.
- Author
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Ma, Shaoqing, Ding, Peng, Zhou, Zhengxuan, Jin, Huilong, Li, Xiaoli, and Li, Yingwei
- Subjects
SUBMILLIMETER waves ,VAN der Waals forces ,MOLECULAR rotation ,BIOMACROMOLECULES - Abstract
Terahertz radiation falls within the spectrum of hydrogen bonding, molecular rotation, and vibration, as well as van der Waals forces, indicating that many biological macromolecules exhibit a strong absorption and resonance in this frequency band. Research has shown that the terahertz radiation of specific frequencies and energies can mediate changes in cellular morphology and function by exciting nonlinear resonance effects in proteins. However, current studies have mainly focused on the cellular level and lack systematic studies on multiple levels. Moreover, the mechanism and law of interaction between terahertz radiation and neurons are still unclear. Therefore, this paper analyzes the mechanisms by which terahertz radiation modulates the nervous system, and it analyzes and discusses the methods by which terahertz radiation modulates neurons. In addition, this paper reviews the laws of terahertz radiation's influence on neuronal morphology and kinetic properties and discusses them in detail in terms of terahertz radiation frequency, energy, and time. In the future, the safety of the terahertz radiation system should be considered first to construct the safety criterion of terahertz modulation, and the spatial resolution of the terahertz radiation system should be improved. In addition, the systematic improvement of the laws and mechanisms of terahertz modulation of the nervous system on multiple levels is the key to applying terahertz waves to neuroscience. This paper can provide a platform for researchers to understand the mechanism of the terahertz–nervous system interaction, its current status, and future research directions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. Psoralen protects neurons and alleviates neuroinflammation by regulating microglial M1/M2 polarization via inhibition of the Fyn-PKCδ pathway.
- Author
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Guo Y, Xu S, Pan X, Xin W, Cao W, Ma W, Li L, Shen Q, and Li Z
- Subjects
- Animals, Mice, PC12 Cells, Rats, Male, Mice, Inbred C57BL, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Cytokines metabolism, Microglia drug effects, Microglia metabolism, Proto-Oncogene Proteins c-fyn metabolism, Protein Kinase C-delta metabolism, Ficusin pharmacology, Ficusin therapeutic use, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Neuroinflammatory Diseases drug therapy, Neuroinflammatory Diseases immunology, Signal Transduction drug effects, Neurons drug effects, Neurons pathology, Lipopolysaccharides
- Abstract
Microglia-mediated neuroinflammation is closely associated with many neurodegenerative diseases. Psoralen has potential for the treatment of many diseases, however, the anti-neuroinflammatory and neuroprotective effects of psoralen have been unclear. This study investigated the anti-neuroinflammatory and neuroprotective effects of psoralen and its regulation of microglial M1/M2 polarization. The LPS-induced mice model was used to test anti-neuroinflammatory effects, regulatory effects on microglia polarization, and neuroprotective effects of psoralen in vivo. The LPS-induced BV2 model was used to test the anti-neuroinflammatory effects and the regulatory effects and mechanisms on microglial M1/M2 polarization of psoralen in vitro. PC12 cell model induced by conditioned medium of BV2 cells was used to validate the protective effects of psoralen against neuroinflammation-induced neuronal damage. These results showed that psoralen inhibited the expression of iNOS, CD86, and TNF-α, and increased the expression of Arg-1, CD206, and IL-10. These results indicated that psoralen inhibited the M1 microglial phenotype and promoted the M2 microglial phenotype. Further studies showed that psoralen inhibited the phosphorylation of Fyn and PKCδ, thereby inhibiting activation of the MAPKs and NF-κB pathways and suppressing the expression of pro-inflammatory cytokines in microglia. Furthermore, psoralen reduced oxidative stress, neuronal damage, and apoptosis via inhibition of neuroinflammation. For the first time, this study showed that psoralen protected neurons and alleviated neuroinflammation by regulating microglial M1/M2 polarization, which may be mediated by inhibition of the Fyn-PKCδ pathway. Thus, psoralen may be a potential agent in the treatment of neuroinflammation-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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40. A single-cell transcriptomic map of the developing Atoh1 lineage identifies neural fate decisions and neuronal diversity in the hindbrain.
- Author
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Butts JC, Wu SR, Durham MA, Dhindsa RS, Revelli JP, Ljungberg MC, Saulnier O, McLaren ME, Taylor MD, and Zoghbi HY
- Subjects
- Animals, Mice, Cell Differentiation, Gene Expression Regulation, Developmental, Neurogenesis genetics, Cell Movement, Rhombencephalon metabolism, Rhombencephalon cytology, Basic Helix-Loop-Helix Transcription Factors metabolism, Basic Helix-Loop-Helix Transcription Factors genetics, Neurons metabolism, Neurons cytology, Cell Lineage genetics, Single-Cell Analysis methods, Transcriptome genetics
- Abstract
Proneural transcription factors establish molecular cascades to orchestrate neuronal diversity. One such transcription factor, Atonal homolog 1 (Atoh1), gives rise to cerebellar excitatory neurons and over 30 distinct nuclei in the brainstem critical for hearing, breathing, and balance. Although Atoh1 lineage neurons have been qualitatively described, the transcriptional programs that drive their fate decisions and the full extent of their diversity remain unknown. Here, we analyzed single-cell RNA sequencing and ATOH1 DNA binding in Atoh1 lineage neurons of the developing mouse hindbrain. This high-resolution dataset identified markers for specific brainstem nuclei and demonstrated that transcriptionally heterogeneous progenitors require ATOH1 for proper migration. Moreover, we identified a sizable population of proliferating unipolar brush cell progenitors in the mouse Atoh1 lineage, previously described in humans as the origin of one medulloblastoma subtype. Collectively, our data provide insights into the developing mouse hindbrain and markers for functional assessment of understudied neuronal populations., Competing Interests: Declaration of interests R.S.D. is a paid consultant for AstraZeneca. H.Y.Z. is a member of the Board of Regeneron, co-founder of Cajal Neuroscience, and on the science advisory board of the Column group. This is work in the Zoghbi Lab and has not been licensed anywhere. The work in this paper has no connection to any of the consulting or companies named here., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
41. Lead exposure induces neurodysfunction through caspase-1-mediated neuronal pyroptosis.
- Author
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Peng D, Wang L, Fang Y, Lu L, Li Z, Jiang S, Chen J, Aschner M, Li S, and Jiang Y
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Male, Dipeptides, para-Aminobenzoates, Pyroptosis drug effects, Caspase 1 metabolism, Neurons drug effects, Neurons pathology, Lead toxicity
- Abstract
Chronic lead (Pb) exposure causes neurodysfunction and contributes to the development of neurodegenerative disease. However, the mechanism of Pb-induced neurological dysfunction have yet to be fully elucidated. This study determined the role pyroptosis plays in Pb-induced neurodysfunction in neurons. We used both in vitro and in vivo approaches to explore whether Pb exposure induces caspase-1-mediated pyroptosis in neurons and its relationship to Pb-induced neurological disorders. Our findings showed that caspase-1-mediated pyroptosis in Pb-exposed neurons activated glycogen synthase kinase 3 protease activity by disrupting Ca
2+ /calmodulin-dependent protein kinase II/cAMP-response element binding protein pathway, leading to neurological disorders. Moreover, the caspase-1 inhibition VX-765 or the non-steroidal anti-inflammatory drug sodium para-aminosalicylic acid (PAS-Na) attenuated the Pb-induced neurological disorders by alleviating caspase-1 mediated neuronal pyroptosis. Our novel studies suggest that caspase-1-mediated pyroptosis in neurons represents a potential mechanism for Pb-induced neurodysfunction, identifying a putative target for attenuating the neurodegenerative effects induced by this metal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
42. Effect of optogenetic excitation of non-orexinergic neurons in the hypothalamic perifornical area on motor behaviors and cardiovascular parameters in rats.
- Author
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Narai E and Koba S
- Subjects
- Animals, Male, Motor Activity physiology, Rats, Orexins metabolism, Orexins genetics, Heart Rate physiology, Blood Pressure physiology, Rats, Sprague-Dawley, Neurons physiology, Neurons metabolism, Optogenetics, Hypothalamus metabolism, Hypothalamus physiology
- Abstract
Central command, a motor volition originating in the rostral part of the brain, plays a pivotal role in the precise regulation of autonomic nervous and cardiovascular systems. Central neuronal substrates responsible for transmitting central command signals remain incompletely understood. This study aimed to investigate the effect of optogenetic excitation of non-orexinergic (NOrx) neurons in the hypothalamic perifornical area (PeFA), where orexinergic neurons are densely distributed, on motor behaviors and cardiovascular parameters in rats. An adeno-associated viral serotype 2 vector carrying the human synapsin promoter encoding channelrhodopsin 2 (ChR2) fused to EYFP was injected into the PeFA of Sprague-Dawley rats, resulting in selective expression of ChR2-EYFP in NOrx PeFA neurons. In conscious rats, optogenetic excitation of NOrx PeFA neurons rapidly elicited walking or biting behavior, simultaneously causing pressor and tachycardiac responses regardless of the observed behavioral patterns. Under anesthesia, this excitation rapidly increased renal sympathetic nerve activity, immediately followed by sympathoinhibition. These findings suggest that NOrx PeFA neurons transmit central command signals, concurrently regulating somatomotor and autonomic nervous systems for locomotor exercise or biting behavior., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
43. Ginsenoside Rg1 alleviates chronic inflammation-induced neuronal ferroptosis and cognitive impairments via regulation of AIM2 - Nrf2 signaling pathway.
- Author
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Kong L, Liu Y, Li J, Wang Y, Ji P, Shi Q, Han M, Xu H, Li W, and Li W
- Subjects
- Animals, Male, Mice, Anti-Inflammatory Agents pharmacology, Cell Line, DNA-Binding Proteins, Inflammation drug therapy, Inflammation metabolism, Lipopolysaccharides toxicity, Mice, Inbred C57BL, Neuroinflammatory Diseases drug therapy, Neuroinflammatory Diseases metabolism, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, NF-E2-Related Factor 2 metabolism, Cognitive Dysfunction drug therapy, Cognitive Dysfunction metabolism, Ferroptosis drug effects, Ginsenosides pharmacology, Neurons drug effects, Neurons metabolism, Signal Transduction drug effects
- Abstract
Ethnopharmacological Relevance: Ginseng is a valuable herb in traditional Chinese medicine. Modern research has shown that it has various benefits, including tonifying vital energy, nourishing and strengthening the body, calming the mind, improving cognitive function, regulating fluids, and returning blood pressure, etc. Rg1 is a primary active component of ginseng. It protects hippocampal neurons, improves synaptic plasticity, enhances cognitive function, and boosts immunity. Furthermore, it exhibits anti-aging and anti-fatigue properties and holds great potential for preventing and managing neurodegenerative diseases (NDDs)., Aim of the Study: The objective of this study was to examine the role of Rg1 in treating chronic inflammatory NDDs and its molecular mechanisms., Materials and Methods: In vivo, we investigated the protective effects of Rg1 against chronic neuroinflammation and cognitive deficits in mice induced by 200 μg/kg lipopolysaccharide (LPS) for 21 days using behavioral tests, pathological sections, Western blot, qPCR and immunostaining. In vitro experiments involved the stimulation of HT22 cells with 10 μg/ml of LPS, verification of the therapeutic effect of Rg1, and elucidation of its potential mechanism of action using H2DCFDA staining, BODIPY™ 581/591 C11, JC-1 staining, Western blot, and immunostaining., Results: Firstly, it was found that Rg1 significantly improved chronic LPS-induced behavioral and cognitive dysfunction in mice. Further studies showed that Rg1 significantly attenuated LPS-induced neuronal damage by reducing levels of IL-6, IL-1β and ROS, and inhibiting AIM2 inflammasome. Furthermore, chronic LPS exposure induced the onset of neuronal ferroptosis by increasing the lipid peroxidation product MDA and regulating the ferroptosis-associated proteins Gpx4, xCT, FSP1, DMT1 and TfR, which were reversed by Rg1 treatment. Additionally, Rg1 was found to activate Nrf2 and its downstream antioxidant enzymes, such as HO1 and NQO1, both in vivo and in vitro. In vitro studies also showed that the Nrf2 inhibitor ML385 could inhibit the anti-inflammatory, antioxidant, and anti-ferroptosis effects of Rg1., Conclusions: This study demonstrated that Rg1 administration ameliorated chronic LPS-induced cognitive deficits and neuronal ferroptosis in mice by inhibiting neuroinflammation and oxidative stress. The underlying mechanisms may be related to the inhibition of AIM2 inflammasome and activation of Nrf2 signaling. These findings provide valuable insights into the treatment of chronic neuroinflammation and associated NDDs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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44. Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.
- Author
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Wu JW, Gao W, Shen LP, Chen YL, Du SQ, Du ZY, Zhao XD, and Lu XJ
- Subjects
- Animals, Mice, Male, Neuroprotective Agents pharmacology, Neuroprotective Agents chemistry, Neuroprotective Agents isolation & purification, Plant Extracts pharmacology, Plant Extracts chemistry, Janus Kinase 1 metabolism, STAT1 Transcription Factor metabolism, Disease Models, Animal, Molecular Docking Simulation, Apoptosis drug effects, Network Pharmacology, Leonurus chemistry, Neurons drug effects, Neurons metabolism, Cerebral Hemorrhage drug therapy
- Abstract
Ethnopharmacological Relevance: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear., Aims of the Study: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH., Materials and Methods: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms., Results: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression., Conclusion: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
45. Biological computations: Limitations of attractor-based formalisms and the need for transients.
- Author
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Koch D, Nandan A, Ramesan G, and Koseska A
- Subjects
- Animals, Humans, Signal Transduction, Models, Biological, Computer Simulation, Models, Neurological, Nerve Net physiology, Neurons physiology
- Abstract
Living systems, from single cells to higher vertebrates, receive a continuous stream of non-stationary inputs that they sense, for e.g. via cell surface receptors or sensory organs. By integrating these time-varying, multi-sensory, and often noisy information with memory using complex molecular or neuronal networks, they generate a variety of responses beyond simple stimulus-response association, including avoidance behavior, life-long-learning or social interactions. In a broad sense, these processes can be understood as a type of biological computation. Taking as a basis generic features of biological computations, such as real-time responsiveness or robustness and flexibility of the computation, we highlight the limitations of the current attractor-based framework for understanding computations in biological systems. We argue that frameworks based on transient dynamics away from attractors are better suited for the description of computations performed by neuronal and signaling networks. In particular, we discuss how quasi-stable transient dynamics from ghost states that emerge at criticality have a promising potential for developing an integrated framework of computations, that can help us understand how living system actively process information and learn from their continuously changing environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
46. The role of glial and neuronal Eph/ephrin signaling in Drosophila mushroom body development and sleep and circadian behavior.
- Author
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Lee JE, Lee H, Baek E, Choi B, Yun HS, Yoo YK, Lee YS, Song GJ, and Cho KS
- Subjects
- Animals, Drosophila Proteins metabolism, Drosophila Proteins genetics, Receptors, Eph Family metabolism, Receptors, Eph Family genetics, Drosophila melanogaster metabolism, Drosophila melanogaster physiology, Drosophila melanogaster genetics, Drosophila metabolism, Neuroglia metabolism, Sleep physiology, Sleep genetics, Circadian Rhythm physiology, Signal Transduction, Neurons metabolism, Ephrins metabolism, Ephrins genetics, Mushroom Bodies metabolism
- Abstract
The Eph receptor, a prototypically large receptor protein tyrosine kinase, interacts with ephrin ligands, forming a bidirectional signaling system that impacts diverse brain functions. Eph receptors and ephrins mediate forward and reverse signaling, affecting neurogenesis, axon guidance, and synaptic signaling. While mammalian studies have emphasized their roles in neurogenesis and synaptic plasticity, the Drosophila counterparts are less studied, especially in glial cells, despite structural similarities. Using RNAi to modulate Eph/ephrin expression in Drosophila neurons and glia, we studied their roles in brain development and sleep and circadian behavior. Knockdown of neuronal ephrin disrupted mushroom body development, while glial knockdown had minimal impact. Surprisingly, disrupting ephrin in neurons or glial cells altered sleep and circadian rhythms, indicating a direct involvement in these behaviors independent from developmental effects. Further analysis revealed distinct sleep phenotypes between neuronal and glial knockdowns, underscoring the intricate interplay within the neural circuits that govern behavior. Glia-specific knockdowns showed altered sleep patterns and reduced circadian rhythmicity, suggesting an intricate role of glia in sleep regulation. Our findings challenge simplistic models of Eph/ephrin signaling limited to neuron-glia communication and emphasize the complexity of the regulatory networks modulating behavior. Future investigations targeting specific glial subtypes will enhance our understanding of Eph/ephrin signaling's role in sleep regulation across species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
47. Aluminum causes irreversible damage to the development of hippocampal neurons by regulating m6A RNA methylation.
- Author
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Yang L, Qi G, Rao W, Cen Y, Chen L, Li W, and Pang Y
- Subjects
- Animals, Female, Mice, Pregnancy, Aluminum toxicity, Methyltransferases genetics, Methyltransferases metabolism, Neurotoxicity Syndromes genetics, Neurotoxicity Syndromes metabolism, Neurotoxicity Syndromes pathology, Neurotoxicity Syndromes etiology, Prenatal Exposure Delayed Effects, Hippocampus drug effects, Hippocampus growth & development, Hippocampus metabolism, Hippocampus pathology, Neurons drug effects, Neurons pathology, Neurons metabolism, RNA Methylation
- Abstract
The underlying mechanism of the aluminum (Al) on neurotoxicity remains unclear. We explored whether the impairment of hippocampal neurons induced by developmental Al exposure was associated with the m6A RNA modification in mice. In this study, the pregnant female mice were administered 4 mg/mL aluminum-lactate from gestational day (GD) 6 to postnatal day (PND) 21. On PND 21, 10 offsprings per group were euthanized by exsanguination from the abdominal aorta after deep anesthetization. The other offsprings which treated with aluminum-lactate on maternal generation were divided into two groups and given 0 (PND60
a ) and 4 mg/mL (PND60b ) aluminum-lactate in their drinking water until PND 60. Significant neuronal injuries of hippocampus as well as a reduction in the m6A RNA modification and the expression of methylase were observed at PND 21 and PND 60a mice. The results indicated that Al-induced developmental neurotoxicity could persist into adulthood despite no sustained Al accumulation. m6A RNA modification had a crucial role in developmental neurotoxicity induced by Al. In addition, Al exposure during the embryonic to adult stages can cause more severe nerve damage and decline of m6A RNA modification. Collectively, these results suggest that the mechanism underlying Al-induced neurotoxicity appears to involve m6A RNA modification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
48. Lavandula angustifolia Mill. inhibits high glucose and nicotine-induced Ca 2+ influx in microglia and neuron-like cells via two distinct mechanisms.
- Author
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Kim YJ, Lee MK, Kim U, Lee JM, Hsieh YS, and Seol GH
- Subjects
- Animals, Oils, Volatile pharmacology, Astrocytes drug effects, Astrocytes metabolism, Rats, Calcium Channel Blockers pharmacology, Cells, Cultured, Nicotine pharmacology, Glucose metabolism, Microglia drug effects, Microglia metabolism, Calcium metabolism, Neurons drug effects, Neurons metabolism, Lavandula
- Abstract
Smoking remains a significant health problem in patients with type 2 diabetes mellitus. This study compared intracellular Ca
2+ ([Ca2+ ]i ) in microglia, neurons, and astrocytes in the presence of high glucose (HG) and nicotine and evaluated the effects of Lavandula angustifolia Mill. essential oil (LEO) on this process. [Ca2+ ]i concentrations were measured by monitoring the fluorescence of Fura-2 acetoxymethyl ester. Treatment with HG and nicotine significantly increased [Ca2+ ]i in both microglia and neurons through Ca2+ influx from extracellular sources. This increased Ca2+ influx in microglia, however, was significantly reduced by LEO, an effect partially inhibited by the Na+ /Ca2+ exchanger (NCX) inhibitor Ni2+ . Ca2+ influx in neuron-like cells pretreated with HG plus nicotine was also significantly decreased by LEO, an effect partially inhibited by the L-type Ca2+ channel blocker nifedipine and the T-type Ca2+ channel blocker mibefradil. LEO or a two-fold increase in the applied number of astrocytes attenuated Ca2+ influx caused by high glucose and nicotine in the mixed cells of the microglia, neuron-like cells and astrocytes. These findings suggest that LEO can regulate HG and nicotine-induced Ca2+ influx into microglia and neurons through two distinct mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)- Published
- 2024
- Full Text
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49. N 6 -methyldeoxyadenosine modification difference contributes to homocysteine-induced mitochondrial perturbation in rat hippocampal primary neurons and PC12 cells.
- Author
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Zhang L, Xie F, Wang X, Sun Z, Hu H, Wu Y, Zhang S, Chen X, Qian L, and Zhao Y
- Subjects
- Animals, Rats, PC12 Cells, Rats, Sprague-Dawley, DNA, Mitochondrial metabolism, DNA, Mitochondrial genetics, Cells, Cultured, Methyltransferases metabolism, Methyltransferases genetics, Neurons metabolism, Neurons drug effects, Homocysteine pharmacology, Homocysteine analogs & derivatives, Homocysteine metabolism, Mitochondria metabolism, Mitochondria drug effects, Deoxyadenosines pharmacology, Hippocampus metabolism, Hippocampus drug effects
- Abstract
Elevated homocysteine (Hcy) levels are detrimental to neuronal cells and contribute to cognitive dysfunction in rats. Mitochondria plays a crucial role in cellular energy metabolism. Interestingly, the damaging effects of Hcy in vivo and in vitro conditions exhibit distinct results. Herein, we aimed to investigate the effects of Hcy on mitochondrial function in primary neurons and PC12 cells and explore the underlying mechanisms involved. The metabolic intermediates of Hcy act as methyl donors and play important epigenetic regulatory roles. N6-methyldeoxyadenosine (6 mA) modification, which is enriched in mitochondrial DNA (mtDNA), can be mediated by methylase METTL4. Our study suggested that mitochondrial perturbation caused by Hcy in primary neurons and PC12 cells may be attributable to mtDNA 6 mA modification difference. Hcy could activate the expression of METTL4 within mitochondria to facilitate mtDNA 6 mA status, and repress mtDNA transcription, then result in mitochondrial dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
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50. Regulated circRNA nuclear export in neuronal differentiation.
- Author
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Li D and Huang Y
- Subjects
- Humans, Animals, Cell Nucleus metabolism, RNA, Circular metabolism, RNA, Circular genetics, Neurons metabolism, Neurons cytology, Active Transport, Cell Nucleus, Cell Differentiation, RNA metabolism
- Abstract
Multiple mechanisms have been reported for how circular RNAs (circRNAs) are exported to the cytoplasm. A recent paper by Cao et al. shows that export of a subset of circRNAs with (A)-rich motifs, including one with a clear function, is regulated during neuronal development via a novel mechanism., Competing Interests: Declaration of interests The authors have no conflicts of interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
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