9 results on '"Altschüler J"'
Search Results
2. Levodopa-Induced Dyskinesia Are Mediated by Cortical Gamma Oscillations in Experimental Parkinsonism.
- Author
-
Güttler C, Altschüler J, Tanev K, Böckmann S, Haumesser JK, Nikulin VV, Kühn AA, and van Riesen C
- Subjects
- Animals, Antiparkinson Agents adverse effects, Disease Models, Animal, Levodopa adverse effects, Oxidopamine toxicity, Rats, Dyskinesia, Drug-Induced etiology, Parkinson Disease, Parkinsonian Disorders chemically induced, Parkinsonian Disorders drug therapy
- Abstract
Background: Levodopa is the most efficacious drug in the symptomatic therapy of motor symptoms in Parkinson's disease (PD); however, long-term treatment is often complicated by troublesome levodopa-induced dyskinesia (LID). Recent evidence suggests that LID might be related to increased cortical gamma oscillations., Objective: The objective of this study was to test the hypothesis that cortical high-gamma network activity relates to LID in the 6-hydroxydopamine model and to identify new biomarkers for adaptive deep brain stimulation (DBS) therapy in PD., Methods: We recorded and analyzed primary motor cortex (M1) electrocorticogram data and motor behavior in freely moving 6-OHDA lesioned rats before and during a daily treatment with levodopa for 3 weeks. The results were correlated with the abnormal involuntary movement score (AIMS) and used for generalized linear modeling (GLM)., Results: Levodopa reverted motor impairment, suppressed beta activity, and, with repeated administration, led to a progressive enhancement of LID. Concurrently, we observed a highly significant stepwise amplitude increase in finely tuned gamma (FTG) activity and gamma centroid frequency. Whereas AIMS and FTG reached their maximum after the 4th injection and remained on a stable plateau thereafter, the centroid frequency of the FTG power continued to increase thereafter. Among the analyzed gamma activity parameters, the fraction of longest gamma bursts showed the strongest correlation with AIMS. Using a GLM, it was possible to accurately predict AIMS from cortical recordings., Conclusions: FTG activity is tightly linked to LID and should be studied as a biomarker for adaptive DBS. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
- Published
- 2021
- Full Text
- View/download PDF
3. Subthalamic beta oscillations correlate with dopaminergic degeneration in experimental parkinsonism.
- Author
-
Haumesser JK, Beck MH, Pellegrini F, Kühn J, Neumann WJ, Altschüler J, Harnack D, Kupsch A, Nikulin VV, Kühn AA, and van Riesen C
- Subjects
- Animals, Deep Brain Stimulation, Electroencephalography, Electrophysiological Phenomena, Hydroxydopamines, Male, Motor Cortex pathology, Movement Disorders pathology, Neostriatum physiopathology, Parkinsonian Disorders chemically induced, Rats, Treatment Outcome, Beta Rhythm, Dopaminergic Neurons pathology, Nerve Degeneration pathology, Parkinsonian Disorders pathology, Subthalamic Nucleus physiopathology
- Abstract
Excessive beta activity has been shown in local field potential recordings from the cortico-basal ganglia loop of Parkinson's disease patients and in its various animal models. Recent evidence suggests that enhanced beta oscillations may play a central role in the pathophysiology of the disorder and that beta activity may be directly linked to the motor impairment. However, the temporal evolution of exaggerated beta oscillations during the ongoing dopaminergic neurodegeneration and its relation to the motor impairment and histological changes are still unknown. We investigated motor behavioral, in-vivo electrophysiological (subthalamic nucleus, motor cortex) and histological changes (striatum, substantia nigra compacta) 2, 5, 10 and 20-30 days after a 6-hydroxydopamine injection into the medial forebrain bundle in Wistar rats. We found strong correlations between subthalamic beta power and motor impairment. No correlation was found for beta power in the primary motor cortex. Only subthalamic but not cortical beta power was strongly correlated with the histological markers of the dopaminergic neurodegeneration. Significantly increased subthalamic beta oscillations could be detected before this increase was found in primary motor cortex. At the latest observation time point, a significantly higher percentage of long beta bursts was found. Our study is the first to show a strong relation between subthalamic beta power and the dopaminergic neurodegeneration. Thus, we provide additional evidence for an important pathophysiological role of subthalamic beta oscillations and prolonged beta bursts in Parkinson's disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
4. Differential effects of levodopa and apomorphine on neuronal population oscillations in the cortico-basal ganglia loop circuit in vivo in experimental parkinsonism.
- Author
-
Kühn J, Haumesser JK, Beck MH, Altschüler J, Kühn AA, Nikulin VV, and van Riesen C
- Subjects
- Animals, Apomorphine pharmacology, Basal Ganglia physiology, Cerebral Cortex physiology, Dose-Response Relationship, Drug, Levodopa pharmacology, Male, Nerve Net physiology, Neurons drug effects, Neurons physiology, Parkinsonian Disorders physiopathology, Rats, Rats, Wistar, Apomorphine therapeutic use, Basal Ganglia drug effects, Cerebral Cortex drug effects, Levodopa therapeutic use, Nerve Net drug effects, Parkinsonian Disorders drug therapy
- Abstract
The current pharmacotherapy of Parkinson's disease (PD) is primarily based on two classes of drugs: dopamine precursors, namely levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents exert their beneficial clinical effects on motor and non-motor symptoms in PD via dopamine receptors, clinical efficiency and side effects differ substantially between levodopa and apomorphine. Levodopa can provide a greater symptomatic relief than dopamine receptor agonists. However, because long-term levodopa use is associated with early debilitating motor fluctuations, dopamine receptor agonists are often recommended in younger patients. The pharmacodynamic basis of these profound differences is incompletely understood. It has been hypothesized that levodopa and dopamine receptor agonists may have diverging effects on beta and gamma oscillations that have been shown to be of importance for the pathophysiology of PD. Here, we used electrophysiological recordings in anesthetized dopamine-intact and dopamine-depleted rats to systemically compare the impact of levodopa or apomorphine on neuronal population oscillations in three nodes of the cortico-basal ganglia loop circuit. Our results showed that levodopa had a higher potency than apomorphine to suppress the abnormal beta oscillations often associated with bradykinesia while simultaneously enhancing the gamma oscillations often associated with increased movement. Our data suggests that the higher clinical efficacy of levodopa as well as some of its side effects, as e.g. dyskinesias may be based on its characteristic ability to modulate beta-/gamma-oscillation dynamics in the cortico-basal ganglia loop circuit., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
5. High-fat diet-induced obesity and insulin resistance are characterized by differential beta oscillatory signaling of the limbic cortico-basal ganglia loop.
- Author
-
Maurer L, Tang H, Haumesser JK, Altschüler J, Kühn AA, Spranger J, and van Riesen C
- Subjects
- Animals, Beta Rhythm, Cerebral Cortex physiopathology, Diet, High-Fat adverse effects, Extremities physiopathology, Humans, Insulin Resistance physiology, Motor Cortex physiopathology, Neural Pathways physiopathology, Obesity etiology, Obesity genetics, Rats, Basal Ganglia physiopathology, Energy Metabolism genetics, Insulin Resistance genetics, Obesity physiopathology
- Abstract
The concept of brain circuit disorders has been proposed for a variety of neuropsychiatric diseases, characterized by pathological disturbances of neuronal networks including changes in oscillatory signaling of re-entrant cortico-subcortical loops in the basal ganglia system. Parts of this circuitry play a pivotal role in energy homeostasis. We therefore investigated whether high-fat diet (HFD) induced obesity is associated with changes in oscillatory signaling in the limbic cortico-basal ganglia loop. We performed multi-site in-vivo electrophysiological recordings of local field potentials within this network under urethane anesthesia in adult rats after 4 weeks of HFD feeding compared to age-matched controls. Recordings were performed at baseline and during systemic glucose challenge. Our analysis demonstrates increased oscillatory beta power in the nucleus accumbens (NAC) associated with decreased beta coherence between cortex and NAC in animals fed a HFD. Spontaneous beta oscillatory power strongly correlated with endocrine markers of obesity. The glucose challenge increased beta oscillations in control animals but not in animals receiving the HFD. Furthermore direct intracerebroventricular insulin injection increased beta oscillations in the NAC. The present study provides evidence for aberrant oscillatory signaling in the limbic cortico-basal ganglia loop that might contribute to the dysfunctional information processing in obesity.
- Published
- 2017
- Full Text
- View/download PDF
6. Short- and long-term dopamine depletion causes enhanced beta oscillations in the cortico-basal ganglia loop of parkinsonian rats.
- Author
-
Beck MH, Haumesser JK, Kühn J, Altschüler J, Kühn AA, and van Riesen C
- Subjects
- Analysis of Variance, Animals, Basal Ganglia drug effects, Beta Rhythm drug effects, Cerebral Cortex drug effects, Disease Models, Animal, Evoked Potentials drug effects, Evoked Potentials physiology, Male, Membrane Potentials drug effects, Membrane Potentials physiology, Motor Activity drug effects, Motor Activity physiology, Neural Pathways drug effects, Neural Pathways physiopathology, Oxidopamine toxicity, Parkinsonian Disorders chemically induced, Parkinsonian Disorders physiopathology, Rats, Rats, Wistar, Spectrum Analysis, Sympatholytics toxicity, Time Factors, Tyrosine 3-Monooxygenase metabolism, Basal Ganglia physiopathology, Beta Rhythm physiology, Cerebral Cortex physiopathology, Dopamine metabolism, Parkinsonian Disorders pathology
- Abstract
Abnormally enhanced beta oscillations have been found in deep brain recordings from human Parkinson's disease (PD) patients and in animal models of PD. Recent correlative evidence suggests that beta oscillations are related to disease-specific symptoms such as akinesia and rigidity. However, this hypothesis has also been repeatedly questioned by studies showing no changes in beta power in animal models using an acute pharmacologic dopamine blockade. To further investigate the temporal dynamics of exaggerated beta synchrony in PD, we investigated the reserpine model, which is characterized by an acute and stable disruption of dopamine transmission, and compared it to the chronic progressive 6-hydroxydopamine (6-OHDA) model. Using simultaneous electrophysiological recordings in urethane anesthetized rats from the primary motor cortex, the subthalamic nucleus and the reticulate part of the substantia, we found evidence for enhanced beta oscillations in the basal ganglia of both animal models during the activated network state. In contrast to 6-OHDA, reserpine treated animals showed no involvement of primary motor cortex. Notably, beta coherence levels between primary motor cortex and basal ganglia nuclei were elevated in both models. Although both models exhibited elevated beta power and coherence levels, they differed substantially in respect to their mean peak frequency: while the 6-OHDA peak was located in the low beta range (17Hz), the reserpine peak was centered at higher beta frequencies (27Hz). Our results further support the hypothesis of an important pathophysiological relation between enhanced beta activity and akinesia in parkinsonism., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
7. Adipose-derived human mesenchymal stem cells induce long-term neurogenic and anti-inflammatory effects and improve cognitive but not motor performance in a rat model of Parkinson's disease.
- Author
-
Schwerk A, Altschüler J, Roch M, Gossen M, Winter C, Berg J, Kurtz A, Akyüz L, and Steiner B
- Subjects
- Amphetamine, Animals, Disease Models, Animal, Dopaminergic Neurons pathology, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus pathology, Humans, Male, Maze Learning, Memory, Short-Term, Mesenchymal Stem Cell Transplantation, Nerve Degeneration pathology, Parkinson Disease pathology, Rats, Wistar, Rotation, Substantia Nigra pathology, Time Factors, Tyrosine 3-Monooxygenase metabolism, Young Adult, Adipose Tissue cytology, Anti-Inflammatory Agents metabolism, Cognition, Mesenchymal Stem Cells cytology, Motor Activity, Neurogenesis, Parkinson Disease physiopathology, Parkinson Disease therapy
- Abstract
Background: Mesenchymal stem cells (MSC) are easily harvested, and possess anti-inflammatory and trophic properties. Furthermore, MSC promote neuroprotection and neurogenesis, which could greatly benefit neurodegenerative disorders, such as Parkinson's disease., Methods: MSC were transplanted one week after 6-hydroxydopamine lesioning and effects were evaluated after 6 months., Results: MSC localized around the substantia nigra and the arachnoid mater, expressing pericyte and endothelial markers. MSC protected dopamine levels and upregulated peripheral anti-inflammatory cytokines. Furthermore, adipose-derived MSC increased neurogenesis in hippocampal and subventricular regions, and boosted memory functioning., Conclusion: Considering that hyposmia and loss of memory function are two major nonmotor symptoms in Parkinson's disease, transplants with modulatory effects on the hippocampus and subventricular zone could provide a disease-modifying therapy.
- Published
- 2015
- Full Text
- View/download PDF
8. Human adipose-derived mesenchymal stem cells improve motor functions and are neuroprotective in the 6-hydroxydopamine-rat model for Parkinson's disease when cultured in monolayer cultures but suppress hippocampal neurogenesis and hippocampal memory function when cultured in spheroids.
- Author
-
Berg J, Roch M, Altschüler J, Winter C, Schwerk A, Kurtz A, and Steiner B
- Subjects
- Adipose Tissue cytology, Adult, Animals, Brain-Derived Neurotrophic Factor genetics, Brain-Derived Neurotrophic Factor metabolism, Cell Differentiation genetics, Cells, Cultured, Disease Models, Animal, Female, Glial Fibrillary Acidic Protein genetics, Glial Fibrillary Acidic Protein metabolism, Hippocampus cytology, Humans, Mesenchymal Stem Cell Transplantation methods, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Microscopy, Confocal, Neurogenesis, Neuroprotection physiology, Oxidopamine, Parkinsonian Disorders chemically induced, Parkinsonian Disorders therapy, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Transplantation, Heterologous, Tyrosine 3-Monooxygenase genetics, Tyrosine 3-Monooxygenase metabolism, Cell Culture Techniques methods, Hippocampus physiology, Memory physiology, Mesenchymal Stem Cells physiology, Motor Activity physiology, Parkinsonian Disorders physiopathology
- Abstract
Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to induce neuroprotective effects in models for Parkinson's disease (PD). However, these effects strongly depend on the most optimal application of the transplant. In the present study we compared monolayer-cultured (aMSC) and spheroid (sMSC) MSC following transplantation into the substantia nigra (SN) of 6-OHDA lesioned rats regarding effects on the local microenvironment, degeneration of dopaminergic neurons, neurogenesis in the hippocampal DG as well as motor and memory function in the 6-OHDA-rat model for PD. aMSC transplantation significantly increased tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) levels in the SN, increased the levels of the glial fibrillary acidic protein (GFAP) and improved motor functions compared to untreated and sMSC treated animals. In contrast, sMSC grafting induced an increased local microgliosis, decreased TH levels in the SN and reduced numbers of newly generated cells in the dentate gyrus (DG) without yet affecting hippocampal learning and memory function. We conclude that the neuroprotective potential of adipose-derived MSC in the rat model of PD crucially depends on the applied cellular phenotype.
- Published
- 2015
- Full Text
- View/download PDF
9. Human adipose-derived mesenchymal stromal cells increase endogenous neurogenesis in the rat subventricular zone acutely after 6-hydroxydopamine lesioning.
- Author
-
Schwerk A, Altschüler J, Roch M, Gossen M, Winter C, Berg J, Kurtz A, and Steiner B
- Subjects
- Adult, Animals, Brain-Derived Neurotrophic Factor biosynthesis, Cell Proliferation drug effects, Cell- and Tissue-Based Therapy, Cells, Cultured, Disease Models, Animal, Female, Humans, Lateral Ventricles cytology, Obesity metabolism, Olfactory Bulb cytology, Oxidopamine adverse effects, Rats, Rats, Wistar, S100 Calcium Binding Protein beta Subunit biosynthesis, Substantia Nigra cytology, Young Adult, Adipose Tissue cytology, Lateral Ventricles growth & development, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells cytology, Neurogenesis physiology, Parkinson Disease therapy
- Abstract
Background Aims: In Parkinson's disease (PD), neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) axis is affected as the result of the lack of dopaminergic innervations reaching the SVZ. This aberrant network has been related to the hyposmia of PD patients, which is an early diagnostic marker of the disease. Consequently, much interest arose in finding mechanisms to modulate the SVZ-OB axis. Direct modulation of this axis could be achieved by transplantation of mesenchymal stromal cells (MSC), as it has been shown in rat and mouse PD models. However, the neurogenic effect of MSC in PD was thus far only analyzed weeks after transplantation, and little is known about effects immediately after transplantation., Methods: We assessed the acute neuroprotective and neurogenic effects of adipose-derived MSC transplanted into the rat substantia nigra in the 6-hydroxydopamine model of PD., Results: Three days after transplantation, subventricular neurogenesis was significantly increased in MSC-transplanted versus non-transplanted animals. Most MSC were found in the region of the substantia nigra and the surrounding arachnoid mater, expressing S100β and brain-derived neurotrophic factor, whereas some MSC showed an endothelial phenotype and localized around blood vessels., Conclusions: The acute neurogenic effects and neurotrophic factor expression of MSC could help to restore the SVZ-OB axis in PD., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.