Human brain tissues from healthy controls and multiple sclerosis patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE123496 | GEO | 2019/04/29
REPOSITORIES: GEO
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Project description:Changes in gene expression that occur across the entire central nervous system (CNS) during disease do not take into account variability from one CNS region to another and can be confounded by alterations in cellular composition during disease. Multiple sclerosis (MS) is characterized by cell proliferation, migration and damage in various cell types in different CNS regions and causes disabilities related to distinct neurological pathways, such as walking, vision and cognition. Here, a cell-specific and region-specific transcriptomic approach was used to determine changes in gene expression in astrocytes derived from spinal cord, cerebellum, cerebral cortex, and hippocampus in the preclinical MS model, chronic experimental autoimmune encephalomyelitis (EAE). RNA sequencing and bioinformatics analysis showed that changes in gene expression pathways in astrocytes differed between neuroanatomic regions. Further, while astrocytes from spinal cord showed increased expression of immune pathway genes during EAE, cholesterol biosynthesis pathway genes were decreased. Translating these findings from the preclinical model to humans, optic nerve from EAE and optic chiasm from MS each showed a significant decrease in cholesterol biosynthesis pathways. Finally, a treatment targeting cholesterol homeostasis in astrocytes was protective in EAE, suggesting a novel neuroprotective strategy for MS. Using a cell-specific and region-specific gene expression approach can provide therapeutically relevant insights into mechanisms underlying specific disabilities in complex multifocal neurological diseases.
2017-12-23 | GSE100329 | GEO
Project description:Changes in gene expression that occur across the entire central nervous system (CNS) during disease do not take into account variability from one CNS region to another and can be confounded by alterations in cellular composition during disease. Multiple sclerosis (MS) is characterized by cell proliferation, migration and damage in various cell types in different CNS regions and causes disabilities related to distinct neurological pathways, such as walking, vision and cognition. Here, a cell-specific and region-specific transcriptomic approach was used to determine changes in gene expression in astrocytes derived from spinal cord, cerebellum, cerebral cortex, and hippocampus in the preclinical MS model, chronic experimental autoimmune encephalomyelitis (EAE). RNA sequencing and bioinformatics analysis showed that changes in gene expression pathways in astrocytes differed between neuroanatomic regions. Further, while astrocytes from spinal cord showed increased expression of immune pathway genes during EAE, cholesterol biosynthesis pathway genes were decreased. Translating these findings from the preclinical model to humans, optic nerve from EAE and optic chiasm from MS each showed a significant decrease in cholesterol biosynthesis pathways. Finally, a treatment targeting cholesterol homeostasis in astrocytes was protective in EAE, suggesting a novel neuroprotective strategy for MS. Using a cell-specific and region-specific gene expression approach can provide therapeutically relevant insights into mechanisms underlying specific disabilities in complex multifocal neurological diseases.
2017-12-23 | GSE100297 | GEO
Project description:Changes in gene expression that occur across the entire central nervous system (CNS) during disease do not take into account variability from one CNS region to another and can be confounded by alterations in cellular composition during disease. Multiple sclerosis (MS) is characterized by cell proliferation, migration and damage in various cell types in different CNS regions and causes disabilities related to distinct neurological pathways, such as walking, vision and cognition. Here, a cell-specific and region-specific transcriptomic approach was used to determine changes in gene expression in astrocytes derived from spinal cord, cerebellum, cerebral cortex, and hippocampus in the preclinical MS model, chronic experimental autoimmune encephalomyelitis (EAE). RNA sequencing and bioinformatics analysis showed that changes in gene expression pathways in astrocytes differed between neuroanatomic regions. Further, while astrocytes from spinal cord showed increased expression of immune pathway genes during EAE, cholesterol biosynthesis pathway genes were decreased. Translating these findings from the preclinical model to humans, optic nerve from EAE and optic chiasm from MS each showed a significant decrease in cholesterol biosynthesis pathways. Finally, a treatment targeting cholesterol homeostasis in astrocytes was protective in EAE, suggesting a novel neuroprotective strategy for MS. Using a cell-specific and region-specific gene expression approach can provide therapeutically relevant insights into mechanisms underlying specific disabilities in complex multifocal neurological diseases.
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Project description:Microglia are brain-resident, myelin-phagocytosing cells, yet their role in lesion initiation in grey and white matter regions in multiple sclerosis (MS) is unclear. We isolated primary microglia from both, occipital cortex and corpus callosum, of 10 MS and 11 control donors and studied their transcriptional profile by RNA sequencing, thereby identifying regional and MS-associated changes. Identification of pathways underlying regional differences showed a relatively increased type I interferon response in cortical grey matter microglia, while white matter microglia more highly expressed NF-κB pathway genes. In normal-appearing white matter MS tissue, lipid metabolism genes were increased, suggesting processing of myelin by microglia already in areas seemingly devoid of MS pathology. Normal-appearing grey matter MS microglia showed increased activation of glycolysis and metal ion homeostasis, possibly reflecting microglia reacting to iron depositions. Notably, expression of genes associated with microglia homeostasis were hardly changed, suggesting that subtle regional changes in MS-associated microglia do not yet affect their resting state.
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Project description:Recently we demonstrated that amoeboid microglia in white matter regions are essential for proper oligodendrocyte homeostasis and myelinogenesis in the first postnatal week of mice. Amoeboid microglia in the corpus callosum change their activation profile already within few days after postnatal day (P)7 and microglia of the cerebellum show similar features to callosal microglia. Here we expanded our previous transcriptional analysis and performed bulk RNA sequencing of microglia during development in a detailed way in P7, P10 and P42 microglia from corpus callosum, cortex and cerebellum. The goal of this study was to identify a specific gene profile for both, white matter and grey matter microglia during development.
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Project description:Purpose: The central nervous system (CNS) possesses intrinsic remyelination capabilities in response to demyelinating injury. However, this remyelination potential is diminished as demyelinating disease such as multiple sclerosis progresses overtime. To better understand myelin repair processes, the goal of this study was to determine temporal transcriptomic changes in cerebral white matter (corpus callosum) and gray matter (cortex and hippocampus) after acute and chronic demyelinating injury. The cuprizone mouse model of de- and remyelination was used for this investigation. Methods: Adult C57BL/6 mice were exposed to cuprizone diet (0.2%) for 3, 5 or 12 weeks followed by returning to normal diet for up to 12 weeks for recovery. Brain regions were dissected for bulk RNA-seq. Conclusion: RNA-seq analyses suggest common and distinct spatiotemporal transcriptional alterations during CNS demyelination and remyelination. Dataset for this study represents the first that covers gene expression landscapes of three brain regions over extended regenerative periods after chronic CNS demyelination.
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