23 results on '"Enrica Boda"'
Search Results
2. Molecular and functional heterogeneity in dorsal and ventral oligodendrocyte progenitor cells of the mouse forebrain in response to DNA damage
- Author
-
Enrica Boda, Martina Lorenzati, Roberta Parolisi, Brian Harding, Gianmarco Pallavicini, Luca Bonfanti, Amanda Moccia, Stephanie Bielas, Ferdinando Di Cunto, and Annalisa Buffo
- Subjects
Oligodendrocyte Precursor Cells ,Mice ,Oligodendroglia ,Prosencephalon ,Multidisciplinary ,Animals ,DNA Damage ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
In the developing mouse forebrain, temporally distinct waves of oligodendrocyte progenitor cells (OPCs) arise from different germinal zones and eventually populate either dorsal or ventral regions, where they present as transcriptionally and functionally equivalent cells. Despite that, developmental heterogeneity influences adult OPC responses upon demyelination. Here we show that accumulation of DNA damage due to ablation of citron-kinase or cisplatin treatment cell-autonomously disrupts OPC fate, resulting in cell death and senescence in the dorsal and ventral subsets, respectively. Such alternative fates are associated with distinct developmental origins of OPCs, and with a different activation of NRF2-mediated anti-oxidant responses. These data indicate that, upon injury, dorsal and ventral OPC subsets show functional and molecular diversity that can make them differentially vulnerable to pathological conditions associated with DNA damage.
- Published
- 2022
3. In vivo silencing of miR‐125a‐3p promotes myelin repair in models of white matter demyelination
- Author
-
Maria P. Abbracchio, Antonio Bertolotto, Francesca Montarolo, Enrica Boda, Annalisa Buffo, Davide Lecca, Davide Marangon, Roberta Parolisi, Simona Perga, Corinna Giorgi, and Camilla Negri
- Subjects
0301 basic medicine ,Encephalomyelitis, Autoimmune, Experimental ,Biology ,Rats, Sprague-Dawley ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Myelin ,Organ Culture Techniques ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,medicine ,Animals ,Humans ,Gene Silencing ,Remyelination ,Cells, Cultured ,Myelin Sheath ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,medicine.disease ,White Matter ,Oligodendrocyte ,Rats ,Cell biology ,Mice, Inbred C57BL ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Animals, Newborn ,Neurology ,Female ,030217 neurology & neurosurgery ,Ex vivo ,Demyelinating Diseases - Abstract
In the last decade, microRNAs have been increasingly recognized as key modulators of glial development. Recently, we identified miR-125a-3p as a new player in oligodendrocyte physiology, regulating in vitro differentiation of oligodendrocyte precursor cells (OPCs). Here, we show that miR-125a-3p is upregulated in active lesions of multiple sclerosis (MS) patients and in OPCs isolated from the spinal cord of chronic experimental autoimmune encephalomyelitis (EAE) mice, but not in those isolated from the spontaneously remyelinating corpus callosum of lysolecithin-treated mice. To test whether a sustained expression of miR-125a-3p in OPCs contribute to defective remyelination, we modulated miR-125a-3p expression in vivo and ex vivo after lysolecithin-induced demyelination. We found that lentiviral over-expression of miR-125a-3p impaired OPC maturation, whereas its downregulation accelerated remyelination. Transcriptome analysis and luciferase reporter assay revealed that these effects are partly mediated by the direct interaction of miR-125a-3p with Slc8a3, a sodium-calcium membrane transporter, and identified novel candidate targets, such as Gas7, that we demonstrated necessary to correctly address oligodendrocytes to terminal maturation. These findings show that miR-125a-3p upregulation negatively affects OPC maturation in vivo, suggest its role in the pathogenesis of demyelinating diseases and unveil new targets for future promyelinating protective interventions.
- Published
- 2020
4. Understanding the effects of air pollution on neurogenesis and gliogenesis in the growing and adult brain
- Author
-
Enrica Boda, Antonello E. Rigamonti, and Valentina Bollati
- Subjects
Adult ,0301 basic medicine ,Neurogenesis ,Synaptogenesis ,Biology ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Air Pollution ,Drug Discovery ,medicine ,Animals ,Humans ,Epigenetics ,Neuroinflammation ,Gliogenesis ,Neurons ,Pharmacology ,Microglia ,Neurotoxicity ,medicine.disease ,Neural stem cell ,030104 developmental biology ,medicine.anatomical_structure ,Prenatal Exposure Delayed Effects ,Female ,Neuroglia ,Neuroscience - Abstract
Exposure to air pollution - and particularly to particulate matter (PM) - is strongly associated with higher risk of neurodevelopmental disorders, poor mental health and cognitive defects. In animal models, disruption of CNS development and disturbances of adult neurogenesis contribute to PM neurotoxicity. Recent studies show that gestational PM exposure not only affects embryonic neurodevelopment, but also disturbs postnatal brain growth and maturation, by interfering with neurogenic/gliogenic events, myelination and synaptogenesis. Similarly, adult neurogenesis is affected at many levels, from neural stem cell amplification up to the maturation and integration of novel neurons in the adult brain parenchyma. The underlying mechanisms are still by and large unknown. Beyond microglia activation and neuroinflammation, recent studies propose a role for novel epigenetic mechanisms, including DNA methylation and extracellular vesicles-associated microRNAs.
- Published
- 2020
5. Myelin and oligodendrocyte lineage cell dysfunctions: New players in the etiology and treatment of depression and stress‐related disorders
- Author
-
Enrica Boda
- Subjects
Neurons ,0303 health sciences ,Lineage (genetic) ,Depression ,business.industry ,General Neuroscience ,fungi ,Stress-related disorders ,Oligodendrocyte ,Neuromodulation (medicine) ,Pathogenesis ,Oligodendroglia ,03 medical and health sciences ,Myelin ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,Antidepressant ,Cell Lineage ,business ,Neuroscience ,Myelin Sheath ,030217 neurology & neurosurgery ,Depression (differential diagnoses) ,030304 developmental biology - Abstract
Depressive disorders are complex, multifactorial disorders that have been traditionally attributed exclusively to neuronal abnormalities. However, recent studies have increased our understanding of the contribution of glial cells-and particularly of oligodendroglia-to the pathogenesis and treatment outcome of depression and stress-related disorders. This review scrutinizes recent studies focusing on the neurosupportive functions exerted by myelin and oligodendrocyte lineage cells and their disruption in depression and stress-related disorders. It also illustrates how myelin and oligodendroglia respond to antidepressants and non-pharmacological treatment alternatives and proposes oligodendroglia-directed approaches as novel therapeutic options for depressive disorders.
- Published
- 2019
6. Exposure to fine particulate matter (PM
- Author
-
Roberta, Parolisi, Francesca, Montarolo, Alessandro, Pini, Sabrina, Rovelli, Andrea, Cattaneo, Antonio, Bertolotto, Annalisa, Buffo, Valentina, Bollati, and Enrica, Boda
- Subjects
Male ,Mice, Inbred C57BL ,Trachea ,Disease Models, Animal ,Mice ,Animals ,Cell Differentiation ,Particulate Matter ,White Matter ,Myelin Sheath ,Demyelinating Diseases - Abstract
Epidemiological studies show a strong association between exposure to air pollution - and particularly to particulate matter (PM) -, increased prevalence of Multiple Sclerosis (MS) and higher rates of hospital admissions for MS and MS relapses. Besides having immunomodulatory effects and sustaining a systemic oxidative-inflammatory response, PM may participate in MS pathogenesis by targeting also Central Nervous System (CNS)-specific processes, such as myelin repair. Here we show that, in a mouse model of lysolecithin-induced demyelination of the subcortical white matter, post-injury exposure to fine PM hampers remyelination, disturbs oligodendroglia differentiation dynamics and promotes astroglia and microglia reactivity. These findings support the view that exposure to fine PM can contribute to demyelinating pathologies by targeting the endogenous regenerative capability of the CNS tissue.
- Published
- 2020
7. Author response for 'Myelin and oligodendrocyte lineage cell dysfunctions: New players in the etiology and treatment of depression and stress‐related disorders'
- Author
-
Enrica Boda
- Subjects
Myelin ,medicine.anatomical_structure ,Lineage (genetic) ,Cell ,Immunology ,Stress-related disorders ,medicine ,Etiology ,Biology ,Depression (differential diagnoses) ,Oligodendrocyte - Published
- 2019
8. KRIT1 loss-mediated upregulation of NOX1 in stromal cells promotes paracrine pro-angiogenic responses
- Author
-
Alessia Zotta, Lorenza Trabalzini, Jasmine Ercoli, Enrica Boda, Irene Schiavo, Saverio Francesco Retta, and Federica Finetti
- Subjects
0301 basic medicine ,Vascular Endothelial Growth Factor A ,Stromal cell ,KRIT1 ,Endothelium ,Neovascularization, Physiologic ,Biology ,Gene mutation ,Dinoprostone ,03 medical and health sciences ,chemistry.chemical_compound ,Paracrine signalling ,0302 clinical medicine ,Antigens, CD ,Cell Movement ,NOX1 ,Paracrine Communication ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Cerebrovascular disease ,KRIT1 Protein ,Cell Proliferation ,CCM ,Mice, Knockout ,NADPH oxidase ,Cerebrovascular disorder ,COX-2 ,PGE2 ,Cell Biology ,Fibroblasts ,Cadherins ,Cell biology ,Up-Regulation ,Vascular endothelial growth factor ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cyclooxygenase 2 ,030220 oncology & carcinogenesis ,Culture Media, Conditioned ,biology.protein ,NADPH Oxidase 1 ,Matrix Metalloproteinase 2 ,Stromal Cells - Abstract
Cerebral cavernous malformation (CCM) is a cerebrovascular disorder of proven genetic origin characterized by abnormally dilated and leaky capillaries occurring mainly in the central nervous system, with a prevalence of 0.3-0.5% in the general population. Genetic studies have identified causative mutations in three genes, CCM1/KRIT1, CCM2 and CCM3, which are involved in the maintenance of vascular homeostasis. However, distinct studies in animal models have clearly shown that CCM gene mutations alone are not sufficient to cause CCM disease, but require additional contributing factors, including stochastic events of increased oxidative stress and inflammation. Consistently, previous studies have shown that up-regulation of NADPH oxidase-mediated production of reactive oxygen species (ROS) in KRIT1 deficient endothelium contributes to the loss of microvessel barrier function. In this study, we demonstrate that KRIT1 loss-of-function in stromal cells, such as fibroblasts, causes the up-regulation of NADPH oxidase isoform 1 (NOX1) and the activation of inflammatory pathways, which in turn promote an enhanced production of proangiogenic factors, including vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2). Furthermore and importantly, we show that conditioned media from KRIT1 null fibroblasts induce proliferation, migration, matrix metalloproteinase 2 (MMP2) activation and VE-cadherin redistribution in wild type human endothelial cells. Taken together, our results demonstrate that KRIT1 loss-of-function in stromal cells affects the surrounding microenvironment through a NOX1-mediated induction and release of angiogenic factors that are able to promote paracrine proangiogenic responses in human endothelial cells, thus pointing to a novel role for endothelial cell-nonautonomous effects of KRIT1 mutations in CCM pathogenesis, and opening new perspectives for disease prevention and treatment.
- Published
- 2019
9. Early phenotypic asymmetry of sister oligodendrocyte progenitor cells after mitosis and its modulation by aging and extrinsic factors
- Author
-
Verdon Taylor, Patrizia Rosa, Maria P. Abbracchio, Silvia Di Maria, Enrica Boda, and Annalisa Buffo
- Subjects
0303 health sciences ,Cell ,Biology ,Phenotype ,Oligodendrocyte ,Cell biology ,stomatognathic diseases ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine.anatomical_structure ,nervous system ,Neurology ,Downregulation and upregulation ,Immunology ,medicine ,Stem cell ,Mitosis ,030217 neurology & neurosurgery ,Cytokinesis ,030304 developmental biology ,Progenitor - Abstract
Oligodendrocyte progenitor cells (OPCs) persist in the adult central nervous system and guarantee oligodendrocyte turnover throughout life. It remains obscure how OPCs avoid exhaustion during adulthood. Similar to stem cells, OPCs could self-maintain by undergoing asymmetric divisions generating a mixed progeny either keeping a progenitor phenotype or proceeding to differentiation. To address this issue, we examined the distribution of stage-specific markers in sister OPCs during mitosis and later after cell birth, and assessed its correlation with distinct short-term fates. In both the adult and juvenile cerebral cortex a fraction of dividing OPCs gives rise to sister cells with diverse immunophenotypic profiles and short-term behaviors. Such heterogeneity appears as cells exit cytokinesis, but does not derive from the asymmetric segregation of molecules such as NG2 or PDGFRa expressed in the mother cell. Rather, rapid downregulation of OPC markers and upregulation of molecules associated with lineage progression contributes to generate early sister OPC asymmetry. Analyses during aging and upon exposure to physiological (i.e., increased motor activity) and pathological (i.e., trauma or demyelination) stimuli showed that both intrinsic and environmental factors contribute to determine the fraction of symmetric and asymmetric OPC pairs and the phenotype of the OPC progeny as soon as cells exit mitosis.
- Published
- 2014
10. Preventive motor training but not progenitor grafting ameliorates cerebellar ataxia and deregulated autophagy in tambaleante mice
- Author
-
Elisa Fucà, Michela Guglielmotto, Ferdinando Rossi, Enrica Boda, Ketty Leto, and Annalisa Buffo
- Subjects
0301 basic medicine ,Mouse ,Cerebellar Ataxia ,Cell Survival ,Green Fluorescent Proteins ,Mice, Transgenic ,Motor Activity ,Neuroprotection ,lcsh:RC321-571 ,Neurodegeneration ,Neurotransplantation ,Purkinje neurons ,03 medical and health sciences ,Purkinje Cells ,0302 clinical medicine ,Neural Stem Cells ,Cerebellum ,medicine ,Autophagy ,Animals ,Survival rate ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Progenitor ,Cerebellar ataxia ,business.industry ,medicine.disease ,Exercise Therapy ,Transplantation ,Disease Models, Animal ,030104 developmental biology ,Neurology ,Cerebellar cortex ,Synapses ,medicine.symptom ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Treatment options for degenerative cerebellar ataxias are currently very limited. A large fraction of such disorders is represented by hereditary cerebellar ataxias, whose familiar transmission facilitates an early diagnosis and may possibly allow to start preventive treatments before the onset of the neurodegeneration and appearance of first symptoms. In spite of the heterogeneous aetiology, histological alterations of ataxias often include the primary degeneration of the cerebellar cortex caused by Purkinje cells (PCs) loss. Thus, approaches aimed at replacing or preserving PCs could represent promising ways of disease management. In the present study, we compared the efficacy of two different preventive strategies, namely cell replacement and motor training. We used tambaleante (tbl) mice as a model for progressive ataxia caused by selective loss of PCs and evaluated the effectiveness of the preventive transplantation of healthy PCs into early postnatal tbl cerebella, in terms of PC replacement and functional preservation. On the other hand, we investigated the effects of motor training on PC survival, cerebellar circuitry and their behavioral correlates. Our results demonstrate that, despite a good survival rate and integration of grafted PCs, the adopted grafting protocol could not alleviate the ataxic symptoms in tbl mice. Conversely, preventive motor training increases PCs survival with a moderate positive impact on the motor phenotype.
- Published
- 2016
11. Posters
- Author
-
Marta Fumagalli, M. Goetz, Annalisa Buffo, Maria P. Abbracchio, L. Dimou, Patrizia Rosa, Francesca Viganò, Roberta Parolisi, and Enrica Boda
- Subjects
0303 health sciences ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine.anatomical_structure ,Neurology ,Cell ,medicine ,Biology ,Receptor ,030217 neurology & neurosurgery ,030304 developmental biology ,Cell biology - Published
- 2011
12. Beyond cell replacement: unresolved roles of NG2-expressing progenitors
- Author
-
Annalisa Buffo and Enrica Boda
- Subjects
Cell type ,business.industry ,General Neuroscience ,Central nervous system ,buffering ,Depolarization ,Neuroprotection ,lcsh:RC321-571 ,myelin ,Myelin ,depolarization ,medicine.anatomical_structure ,nervous system ,Neuromodulation ,Perspective Article ,neuromodulation ,medicine ,Premovement neuronal activity ,neuroprotection ,Progenitor cell ,Brain Injury ,business ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Neuroscience - Abstract
NG2-expressing parenchymal precursors (NG2+p) serve as primary source of myelinating oligodendrocytes in both the developing and adult Central Nervous System (CNS). However, their abundance, limited differentiation potential at adult stages along with stereotypic reaction to injury independent of the extent of myelin loss suggest that NG2+p exert functions additional to myelin production. In support of this view, NG2+p express a complex battery of molecules known to exert neuromodulatory and neuroprotective functions. Further, they establish intimate physical associations with the other CNS cell types, receive functional synaptic contacts and possess ion channels apt to constantly sense the electrical activity of surrounding neurons. These latter features could endow NG2+p with the capability to affect neuronal functions with potential homeostatic outcomes. Here we summarize and discuss current evidence favoring the view that NG2+p can participate in circuit formation, modulate neuronal activity and survival in the healthy and injured CNS, and propose perspectives for studies that may complete our understanding of NG2+p roles in physiology and pathology.
- Published
- 2014
13. Immune System Modulation of Germinal and Parenchymal Neural Progenitor Cells in Physiological and Pathological Conditions
- Author
-
Annalisa Buffo, Chiara Rolando, and Enrica Boda
- Subjects
chemical and pharmacologic phenomena ,biochemical phenomena, metabolism, and nutrition ,Biology ,Blood–brain barrier ,Major histocompatibility complex ,Neural stem cell ,medicine.anatomical_structure ,Lymphatic system ,Immune system ,Antigen ,Immune privilege ,Immunology ,medicine ,biology.protein ,bacteria ,Antigen-presenting cell - Abstract
Historically, the Central Nervous System (CNS) was considered as an immune privileged site (Billingham and Boswell, 1953), being viewed as a territory physiologically out of the competence of immune cells. This notion has developed on initial studies showing that: (i) CNS unrelated antigens (i.e. foreign grafts, bacteria, viruses) evade an immune recognition when delivered to the brain parenchyma (Galea et al., 2007); (ii) no infiltrating immune cells nor antigen presenting cells (APCs, i.e. dendritic cells, DCs, see Table 1) can be detected in the CNS parenchyma in physiological conditions (Engelhardt and Ransohoff, 2005); (iii) CNS cells do not constitutively express major histocompatibility complex (MHC)I and MHCII molecules (Fabry et al., 1994); (iv) neural cells express apoptosis inductors for immune cells (Bechmann et al., 1999); (v) the CNS does not possess lymphatic vessels (Engelhardt and Ransohoff, 2005). The segregation between nervous and immune cells appeared tightly preserved by the anatomical separations offered by the Blood Brain Barrier (BBB) and the blood-cerebrospinal fluid barrier (Choi and Benveniste, 2004). Over time, on the basis of the association between immune inflammation and neurodegeneration, the concept of immune privilege further acquired the connotation of a defence mechanism against the detrimental effects of immune activation within the CNS.
- Published
- 2012
14. Brain expression of Kv3 subunits during development, adulthood and aging and in a murine model of Alzheimer's disease
- Author
-
Alessandro Pini, Enrica Boda, Francesca Montarolo, Eriola Hoxha, and Filippo Tempia
- Subjects
Cerebellum ,Aging ,Mouse ,Protein subunit ,Hippocampus ,Mice, Inbred Strains ,Mice, Transgenic ,Biology ,Development ,Potassium channels ,Cellular and Molecular Neuroscience ,Mice ,Western blot ,Alzheimer Disease ,medicine ,Animals ,Regulation of gene expression ,Neocortex ,medicine.diagnostic_test ,Wild type ,Gene Expression Regulation, Developmental ,General Medicine ,Olfactory bulb ,Cell biology ,Real-time RT-PCR ,Disease Models, Animal ,medicine.anatomical_structure ,Kv3 ,Alzheimer’s disease ,Shaw Potassium Channels ,Female ,Neuroscience - Abstract
In neurons, voltage-dependent Kv3 potassium channels are essential for the generation of action potentials at high frequency. A dysregulation of the Kv3.1 and Kv3.4 channel subunits has been suggested to contribute to neuronal and glial alterations in Alzheimer's disease, but a quantitative evaluation of these subunits in a mouse model of the pathology is still lacking. We analysed the profile of expression of the four Kv3 subunits by quantitative reverse transcription PCR and Western blot in the whole mouse brain and in dissected brain regions (olfactory bulb, septum, neocortex, hippocampus, brainstem and cerebellum) from 14 days after conception to 18 months after birth. In addition, we measured the levels of Kv3.1 and Kv3.4 messenger RNAs (mRNAs) and proteins in neocortex and hippocampus of APPPS1 mice, a transgenic model of Alzheimer's disease. Although all Kv3 transcripts were significantly expressed in embryonic age in whole brain extracts, only Kv3.1, Kv3.2 and Kv3.4 subunit proteins were present, suggesting a novel role for Kv3 channels at this developmental stage. With the exception of Kv3.4, during postnatal development, Kv3 transcripts and proteins showed a progressive increase in expression and reached an asymptote in adulthood, suggesting that the increase in Kv3 expression during development might contribute to the maturation of the electrical activity of neurons. During aging, Kv3 expression was rather stable. In contrast, in the neocortex of aged APPPS1 mice, Kv3.1 mRNA and protein levels were significantly lower compared to wild type, suggesting that a decrease in Kv3 currents could play a role in the cognitive symptoms of Alzheimer's disease.
- Published
- 2011
15. The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides
- Author
-
Ferdinando Di Cunto, F. Bianchi, Ylenia Bosio, Stefano Taraglio, Gaia Berto, Paola Camera, Daniele Imperiale, Ugo Ala, Filippo Tempia, Frank M. LaFerla, Enrica Boda, Carlos G. Dotti, Antonio Migheli, and Salvatore Oddo
- Subjects
Male ,Mouse ,Fluorescent Antibody Technique ,lcsh:Medicine ,Plaque, Amyloid ,Hippocampus ,Immunoenzyme Techniques ,Amyloid beta-Protein Precursor ,Mice ,Neurobiology of Disease and Regeneration ,Amyloid precursor protein ,Medicine and Health Sciences ,Interactor ,RNA, Small Interfering ,alzheimers-disease ,lcsh:Science ,Cells, Cultured ,database ,Oligonucleotide Array Sequence Analysis ,Neurons ,a-beta ,Multidisciplinary ,precursor protein ,Reverse Transcriptase Polymerase Chain Reaction ,P3 peptide ,Brain ,Neurodegenerative Diseases ,Animal Models ,molecular chaperone ,Cell biology ,Cross-Linking Reagents ,Neurology ,Medicine ,protease inhibitor domain ,Collagen ,Alzheimer's disease ,Research Article ,mice ,Amyloid ,Immunoprecipitation ,brain ,Blotting, Western ,Enzyme-Linked Immunosorbent Assay ,Biology ,Model Organisms ,Alzheimer Disease ,mental disorders ,expression ,medicine ,Animals ,Humans ,RNA, Messenger ,HSP47 Heat-Shock Proteins ,Cell Proliferation ,Amyloid beta-Peptides ,Gene Expression Profiling ,Endoplasmic reticulum ,lcsh:R ,endoplasmic-reticulum ,Embryo, Mammalian ,medicine.disease ,Molecular biology ,Rats ,Disease Models, Animal ,Cellular Neuroscience ,Chaperone (protein) ,biology.protein ,Dementia ,lcsh:Q ,Molecular Neuroscience ,Biomarkers ,HeLa Cells ,Molecular Chaperones ,Neuroscience - Abstract
Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques.
- Published
- 2011
16. The GPR17 receptor in NG2 expressing cells: focus on in vivo cell maturation and participation in acute trauma and chronic damage
- Author
-
Maria P. Abbracchio, Enrica Boda, Patrizia Rosa, Vivien Labat-Gest, Francesca Viganò, Filippo Tempia, Leda Dimou, Marta Fumagalli, and Annalisa Buffo
- Subjects
glial reactivity ,Population ,Primary Cell Culture ,Golgi Apparatus ,Nerve Tissue Proteins ,Brain damage ,Biology ,Receptors, G-Protein-Coupled ,Cellular and Molecular Neuroscience ,Myelin ,Mice ,NG2+ cells ,medicine ,Animals ,Progenitor cell ,Antigens ,education ,Mitosis ,oligodendrocyte development ,demyelination ,mouse neocortex ,Progenitor ,education.field_of_study ,Stem Cells ,Cell Differentiation ,Cell cycle ,Oligodendrocyte ,Cell biology ,Nerve Regeneration ,Mice, Inbred C57BL ,Disease Models, Animal ,Oligodendroglia ,medicine.anatomical_structure ,nervous system ,Neurology ,Brain Injuries ,Acute Disease ,Brain Damage, Chronic ,Proteoglycans ,medicine.symptom ,Neuroscience ,Biomarkers - Abstract
NG2-expressing cells comprise a population of cycling precursors that can exit the cell cycle and differentiate into mature oligodendrocytes. As a whole, they display heterogeneous properties and behaviors that remain unresolved at the molecular level, although partly interpretable as distinct maturation stages. To address this issue, we analyzed the expression of the GPR17 receptor, recently shown to decorate NG2-expressing cells and to operate as an early sensor of brain damage, in immature and adult oligodendrocyte progenitors in the intact brain and after injury. In both the early postnatal and adult cerebral cortex, distinct GPR17 protein localizations and expression levels define different stages of oligodendroglial maturation, ranging from the precursor phase to the premyelinating phenotype. As soon as cells exit mitosis, a fraction of NG2-expressing cells displays accumulation of GPR17 protein in the Golgi apparatus. GPR17 expression is subsequently upregulated and distributed to processes of cells that stop dividing, progressively lose NG2 positivity and assume premyelinating features. Absence of colabeling with mature markers or myelin proteins indicates that GPR17 is downregulated when cells complete their final maturation. BrdU-based fate-mapping demonstrated that a significant fraction of newly generated oligodendrocyte progenitors transiently upregulates GPR17 during maturation. Importantly, we also found that GPR17 does not participate to the early reaction of NG2-expressing cells to damage, while it is induced at postacute stages after injury. These findings identify GPR17 as a marker for progenitor progression within the oligodendroglial lineage and highlight its participation to postacute reactivity of NG2 cells in different injury paradigms.
- Published
- 2010
17. Expression of the new P2Y-like receptor GPR17 during oligodendrocyte precursor cell maturation regulates sensitivity to ATP-induced death
- Author
-
Silvia Ferrario, G. Magni, Patrizia Rosa, Maria P. Abbracchio, Francesca Viganò, Annalisa Buffo, Stefania Ceruti, Marta Boccazzi, and Enrica Boda
- Subjects
Extracellular nucleotides ,Growth factors Oligodendrocytes ,Nerve Tissue Proteins ,Biology ,Receptors, G-Protein-Coupled ,Cellular and Molecular Neuroscience ,Mice ,Receptors, Purinergic P2Y1 ,Adenosine Triphosphate ,Adenine nucleotide ,Precursor cell ,Extracellular ,Animals ,Receptor ,Cells, Cultured ,Regulation of gene expression ,Differentiation ,GPR17 ,Cell Death ,Stem Cells ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Molecular biology ,Phenotype ,Neural stem cell ,Coculture Techniques ,Mice, Inbred C57BL ,Oligodendroglia ,Neurology ,Animals, Newborn ,Uracil nucleotide - Abstract
The P2Y-like receptor GPR17 is expressed by adult neural progenitor cells, suggesting a role in lineage determination. Here, we characterized GPR17 expression and function in mouse cortical primary astrocytes/precursor cell cultures. GPR17 is expressed by a subpopulation of oligodendrocyte precursor cells (OPCs), but not by astrocytes. This expression pattern was also confirmed in vivo. In vitro, GPR17 expression was markedly influenced by culturing conditions. In the presence of growth factors (GFs), no significant GPR17 expression was found. When cultures were shifted to a differentiating medium, a dramatic, time-dependent increase in the number of highly branched GPR17-positive cells was observed. Under these conditions, GPR17 was induced in the totality of O4-positive immature oligodendrocytes. Instead, in cultures originally grown in the absence of GFs, GPR17 was already expressed in morphologically more mature OPCs. Shifting of these cultures to differentiating conditions induced GPR17 only in a subpopulation of O4-positive cells. Under both culture protocols, appearance of more mature CNPase- and MBP-positive cells was associated to a progressive loss of GPR17. GPR17 expression also sensitized cells to adenine nucleotide-induced cytotoxicity, whereas activation with uracil nucleotides promoted differentiation towards a more mature phenotype. We suggest that GFs may keep OPCs in a less differentiated stage by restraining GPR17 expression, and that, under permissive conditions, GPR17 contributes to OPCs differentiation. However, upon high extracellular adenine nucleotide concentrations, as during trauma and ischemia, GPR17 sensitizes cells to cytotoxicity. This double-edged sword role may be exploited to unveil new therapeutic approaches to acute and chronic brain disorders.
- Published
- 2010
18. P4‐203: The P2Y‐like GPR17 receptor participates in oligodendrocyte precursor cell reaction in a model of chronic cerebral amyloidosis
- Author
-
Annalisa Buffo, Patrizia Rosa, Enrica Boda, Filippo Tempia, Eriola Hoxha, Maria P. Abbracchio, and Francesca Montarolo
- Subjects
Epidemiology ,Chemistry ,Health Policy ,Amyloidosis ,Oligodendrocyte progenitor ,medicine.disease ,Cell biology ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Receptor ,Neuroscience - Published
- 2009
19. P4‐010: Time course of intra‐ and extracellular amyloidosis in a murine model of Alzheimer's disease
- Author
-
Enrica Boda, Francesca Montarolo, Eriola Hoxha, and Filippo Tempia
- Subjects
Pathology ,medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Amyloidosis ,Disease ,medicine.disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Murine model ,Time course ,Extracellular ,Medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business - Published
- 2009
20. P4‐009: Delayed motor learning and cerebellar electrophysiological alterations in a murine model of Alzheimer's disease with massive amyloidosis
- Author
-
Eriola Hoxha, Filippo Tempia, Francesca Montarolo, and Enrica Boda
- Subjects
Pathology ,medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Amyloidosis ,Disease ,medicine.disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Electrophysiology ,Developmental Neuroscience ,Murine model ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Motor learning ,business ,Neuroscience - Published
- 2009
21. Selection of reference genes for quantitative real-time RT-PCR studies in mouse brain
- Author
-
Eriola Hoxha, Roberta Parolisi, Filippo Tempia, Enrica Boda, and Alessandro Pini
- Subjects
Molecular Sequence Data ,Gene Expression ,reference genes ,Computational biology ,Biology ,Cellular and Molecular Neuroscience ,Mice ,quantitative real-time RT-PCR ,Pregnancy ,Reference genes ,Gene expression ,medicine ,Animals ,Gene ,Genetics ,Neocortex ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Brain ,General Medicine ,Reference Standards ,Olfactory bulb ,Housekeeping gene ,Gene expression profiling ,medicine.anatomical_structure ,Real-time polymerase chain reaction ,mouse brain ,Female - Abstract
Since a growing number of studies based on the real-time reverse transcriptase polymerase chain reaction (RT-PCR) continue to be published in order to highlight genes specifically involved in brain development, maturation, and function, the identification of reference genes suitable for this kind of experiments is now an urgent need in the neuroscience field. The aim of this work was to verify the suitability of some very common housekeeping genes (such as Gapdh, 18s, and B2m) and of some relatively new control genes (such as Pgk1, Tfrc, and Gusb) during mouse brain maturation. We tested the candidate reference genes in mouse whole brain, cerebellum, brain stem, hippocampus, medial septum, frontal neocortex, and olfactory bulb. Moreover, we reported the first complete study of Pgk1 expression throughout the development and the aging of mouse brain. Although no tested gene showed to be the optimal reference for all mouse brain regions, in general, the new housekeeping genes were highly stable in most of the analyzed regions. Above all, with few exceptions, Pgk1 showed to be a reliable control for the analyzed mouse brain regions during development, maturation, and aging.
- Published
- 2008
22. Stathmin expression modulates migratory properties of GN-11 neurons in vitro
- Author
-
Giovanna Gambarotta, Paolo Giacobini, Costanza Giampietro, Federico Luzzati, Isabelle Perroteau, Enrica Boda, and Aldo Fasolo
- Subjects
medicine.medical_specialty ,Motility ,Stathmin ,macromolecular substances ,Gonadotropin-releasing hormone ,Biology ,migration ,Transfection ,Cell Line ,Gonadotropin-Releasing Hormone ,Mice ,Endocrinology ,Cell Movement ,Internal medicine ,medicine ,Animals ,stathmin ,GnRH neurons ,Cell Aggregation ,Cell Proliferation ,Neurons ,Messenger RNA ,Basal forebrain ,Cadherin ,Chemotaxis ,Phosphoproteins ,medicine.anatomical_structure ,Cell culture ,biology.protein ,Microtubule Proteins ,Neuron - Abstract
Expression of stathmin, a microtubule-associated cytoplasmic protein, prominently localized in neuroproliferative zones and neuronal migration pathways in brain, was investigated in the GnRH neuroendocrine system in vivo and the function was analyzed using an in vitro approach. Here we present novel data demonstrating that GnRH migrating neurons in nasal regions and basal forebrain areas of mouse embryos express stathmin protein. In addition, this expression pattern is dependent on location, as GnRH neurons reaching the hypothalamus are stathmin negative. Immortalized GN-11 cells, which retain many characteristics of migrating GnRH neurons, strongly express stathmin mRNA and protein. The role of stathmin in GnRH migratory properties was evaluated using GN-11 cell line. We up-regulated [stathmin-transfected clones (STMN)+] and down-regulated (STMN-) the expression of stathmin in GN-11 cells, and we investigated changes in cell morphology and motility in vitro. Cells overexpressing stathmin assume a spindle-shaped morphology and their proliferation, as well as their motility, is higher with respect to parental cells. Furthermore, they do not aggregate and express low levels of cadherins compared with control cells. STMN- GN-11 cells are endowed with multipolar processes, and they show a decreased motility and express high levels of cadherin protein. Our findings suggest that stathmin plays a permissive role in GnRH cell motility, possibly via modulation of cadherins expression.
- Published
- 2004
23. Excitability and synaptic alterations in the cerebellum of APP/PS1 mice
- Author
-
Filippo Tempia, Roberta Parolisi, Enrica Boda, Eriola Hoxha, and Francesca Montarolo
- Subjects
Cerebellum ,Mouse ,Postsynaptic Current ,lcsh:Medicine ,Biochemistry ,Synaptic Transmission ,Mice ,Purkinje Cells ,Postsynaptic potential ,Neurobiology of Disease and Regeneration ,lcsh:Science ,gamma-Aminobutyric Acid ,Multidisciplinary ,Glutamate receptor ,Neurochemistry ,Climbing fiber ,Anatomy ,Animal Models ,Alzheimer's disease ,action potential firing ,medicine.anatomical_structure ,Neurology ,Cerebellar cortex ,GABAergic ,Medicine ,Neurochemicals ,Glutamate ,Research Article ,Purkinje cell ,Neurophysiology ,Glutamic Acid ,Mice, Transgenic ,Biology ,Neurotransmission ,Model Organisms ,Alzheimer Disease ,Interneurons ,medicine ,Animals ,Amyloid beta-Peptides ,APP/PS1 mouse ,lcsh:R ,Alzheimer's disease, APP/PS1 mouse, Purkinje cell, cerebellum, GABAergic, glutamatergic ,Disease Models, Animal ,nervous system ,lcsh:Q ,Dementia ,Neuroscience ,glutamatergic - Abstract
In Alzheimer's disease (AD), the severity of cognitive symptoms is better correlated with the levels of soluble amyloid-beta (Aβ) rather than with the deposition of fibrillar Aβ in amyloid plaques. In APP/PS1 mice, a murine model of AD, at 8 months of age the cerebellum is devoid of fibrillar Aβ, but dosage of soluble Aβ(1-42), the form which is more prone to aggregation, showed higher levels in this structure than in the forebrain. Aim of this study was to investigate the alterations of intrinsic membrane properties and of synaptic inputs in Purkinje cells (PCs) of the cerebellum, where only soluble Aβ is present. PCs were recorded by whole-cell patch-clamp in cerebellar slices from wild-type and APP/PS1 mice. In APP/PS1 PCs, evoked action potential discharge showed enhanced frequency adaptation and larger afterhyperpolarizations, indicating a reduction of the intrinsic membrane excitability. In the miniature GABAergic postsynaptic currents, the largest events were absent in APP/PS1 mice and the interspike intervals distribution was shifted to the left, but the mean amplitude and frequency were normal. The ryanodine-sensitive multivescicular release was not altered and the postsynaptic responsiveness to a GABA(A) agonist was intact. Climbing fiber postsynaptic currents were normal but their short-term plasticity was reduced in a time window of 100-800 ms. Parallel fiber postsynaptic currents and their short-term plasticity were normal. These results indicate that, in the cerebellar cortex, chronically elevated levels of soluble Aβ(1-42) are associated with alterations of the intrinsic excitability of PCs and with alterations of the release of GABA from interneurons and of glutamate from climbing fibers, while the release of glutamate from parallel fibers and all postsynaptic mechanisms are preserved. Thus, soluble Aβ(1-42) causes, in PCs, multiple functional alterations, including an impairment of intrinsic membrane properties and synapse-specific deficits, with differential consequences even in different subtypes of glutamatergic synapses.
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.