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Transcriptomic and Functional Studies Reveal Undermined Chemotactic and Angiostimulatory Properties of Aged Microglia During Stroke Recovery

ABSTRACT: Transcriptomic and Functional Studies Reveal Undermined Chemotactic and Angiostimulatory Properties of Aged Microglia During Stroke Recovery

PROVIDER: PRJNA596754 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10741019.fastq.gz	Fastqsanger.gz
	SRR10741020.fastq.gz	Fastqsanger.gz
	SRR10741021.fastq.gz	Fastqsanger.gz
	SRR10741022.fastq.gz	Fastqsanger.gz
	SRR10741023.fastq.gz	Fastqsanger.gz

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Transcriptomic and Functional Studies Reveal Undermined Chemotactic and Angiostimulatory Properties of Aged Microglia During Stroke Recovery

Project description:Age-dependent alterations in microglia behavior have been implicated in neurodegeneration and CNS injuries. Here, we compared the transcriptional profiles of young versus aged microglia during stroke recovery. CD45intermediateCD11b+ microglia were FACS-isolated from the brains of young (10-week-old) and aged (18-month-old) male mice 14 days after distal middle cerebral artery occlusion (dMCAO) or sham operation and subjected to RNA-sequencing analysis. Functional groups enriched in young microglia are indicative of upregulation in cell movement, cell interactions, inflammatory responses and angiogenesis, while aged microglia exhibited a reduction or no change in these features. We confirmed reduced chemoattractive capacities of aged microglia toward ischemic brain tissue in organotypic slide co-cultures, and delayed accumulation of aged microglia around dead neurons injected into the striatum in vivo. In addition, aging is associated with an overall failure to increase the expression of microglial genes involved in cell-cell interactions, such as CXCL10. Finally, impaired upregulation of pro-angiogenic genes in aged microglia was associated with a decline in neovascularization in aged mice compared to young mice after dMCAO. This study provides a new resource to understand the mechanisms underlying microglial alterations in the aged brain milieu and sheds light on new strategies to improve microglial functions in aged stroke victims.

2020-01-31 | GSE142361 | GEO

Transcriptomic and functional studies reveal undermined chemotactic and angiostimulatory properties of aged microglia during stroke recovery.

Project description:Age-dependent alterations in microglia behavior have been implicated in neurodegeneration and CNS injuries. Here, we compared the transcriptional profiles of young versus aged microglia during stroke recovery. CD45intermediateCD11b+ microglia were FACS-isolated from the brains of young (10-week-old) and aged (18-month-old) male mice with sham operation or 14 days after distal middle cerebral artery occlusion and subjected to RNA-sequencing analysis. Functional groups enriched in young microglia are indicative of upregulation in cell movement, cell interactions, inflammatory responses and angiogenesis, while aged microglia exhibited a reduction or no change in these features. We confirmed reduced chemoattractive capacities of aged microglia toward ischemic brain tissue in organotypic slide co-cultures, and delayed accumulation of aged microglia around dead neurons injected into the striatum in vivo. In addition, aging is associated with an overall failure to increase the expression of microglial genes involved in cell-cell interactions, such as CXCL10. Finally, impaired upregulation of pro-angiogenic genes in aged microglia was associated with a decline in neovascularization in aged mice compared to young mice after distal middle cerebral artery occlusion. This study provides a new resource to understand the mechanisms underlying microglial alterations in the aged brain milieu and sheds light on new strategies to improve microglial functions in aged stroke victims.

| S-EPMC7687033 | biostudies-literature

CREB Controls Cortical Circuit Plasticity and Functional Recovery after Stroke

Project description:Treatments that stimulate neuronal excitability enhance motor performance after stroke.cAMP-response-element binding protein (CREB) is a transcription factor that plays a key rolein neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool ofmotor neurons enhances motor recovery after stroke, while blocking CREB signaling preventsstroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with thehM4di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue,demonstrating that it is possible to turn off and on stroke recovery by manipulating theactivity of CREB-transfected neurons. CREB transfection enhances re-mapping of injuredsomatosensory and motor circuits, and induces the formation of new connections withinthese circuits. CREB is a central molecular node in the circuit responses after stroke that leadto recovery from motor deficits.

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microRNAs involved in regulating embolic stroke recovery following spontaneous reperfusion [miRNA]

Project description:To date, miRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models. In this study presented here, Middle Cerebral Artery Occlusion stroke model was established by using embolus and the brain samples of stroke model were harvested at 0hrs, 3hrs, 6hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs and 168hrs. RNAs were extracted from these samples and microRNA array and mRNA array were performed.

2013-12-09 | E-GEOD-46266 | biostudies-arrayexpress

microRNAs involved in regulating embolic stroke recovery following spontaneous reperfusion [mRNA]

Project description:To date, miRNA and mRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models. In this study presented here, Middle Cerebral Artery Occlusion stroke model was established by using embolus and the brain samples of stroke model were harvestd at 0hrs, 3hrs, 6hrs, 12hrs, 24hrs, 48hrs, 72hrs, 120hrs and 168hrs. RNAs were extracted from these samples and microRNA array and mRNA array were performed.

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Activity-dependent Transcriptional Programs in Memory Regulate Motor Recovery after Stroke

Project description:Stroke causes death of brain tissue leading to long-term deficits. Behavioral evidence from neurorehabilitative therapies suggest learning-induced neuroplasticity can lead to beneficial outcomes. However, molecular and cellular mechanisms that link learning and stroke recovery are unknown. We show that in mouse models of stroke, with enhanced recovery of function from genetic perturbations of learning and memory genes, express activity-dependent transcriptional programs that are normally active during formation or storage of new memories. The expression of neuronal activity-dependent genes are predictive of recovery and occupy a molecular latent space unique to motor recovery. With motor recovery, networks of activity-dependent genes are co-expressed with their transcription factor targets forming gene regulatory networks that support activity-dependent transcription, that are normally diminished after stroke. Neuronal activity-dependent changes at the circuit level are influenced by interactions with microglia. At the molecular level, we show that enrichment of activity-dependent programs in neurons lead to transcriptional changes in microglia where they differentially interact to support intercellular signaling pathways for axon guidance, growth and synaptogenesis. Together, these studies identify activity-dependent transcriptional programs as a fundamental mechanism for neural repair post-stroke.

2024-06-25 | GSE270766 | GEO

Photothrombotic Cerebral Stroke as a Model of Post-Stroke Seizures/Epilepsy in aged mice

Project description:Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility and brain injury using combined behavioral (video) and EEG monitoring and histological (MRI) assessments. To investigate GABAA receptor-mediated convulsive/non-convulsive seizures, lower-doses of pentylenetetrazol (PTZ) was injected. PTZ susceptibility in aging mice increased compared to young adults. One month after PT stroke, aged PT stroke mice exhibited severe convulsive seizures (late-onset). These findings exhibited the increase of GABAA receptor-mediated seizures susceptibility in PT stroke aging mice, but not in young adults.

2023-11-27 | GSE241528 | GEO

Trained immunity induced by high salt diet impedes stroke recovery

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Short-chain fatty acids improve post-stroke recovery via immunological mechanisms.

Project description:This transcriptomic study investigates the effect of therapeutic short-chain fatty acids (SCFA) administration on post-stroke recovery.

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microRNAs involved in regulating embolic stroke recovery following spontaneous reperfusion [miRNA]

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