首页|Activation of glutamatergic neurons in the somatosensory cortex promotes remyelination in ischemic vascular dementia

Activation of glutamatergic neurons in the somatosensory cortex promotes remyelination in ischemic vascular dementia

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Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia,how-ever no effective treatments are available.Here,based on magnetic resonance imaging studies of patients with white matter damage,we found that this damage is associated with disorganized cortical structure.In a mouse model,optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligo-dendrocyte progenitor cell(OPC)proliferation,remyelination in the corpus callosum,and recovery of cognitive ability after cerebral hypoperfusion.The therapeutic effect of such stimulation was restricted to the upper layers of the cortex,but also spanned a wide time window after ischemia.Mechanistically,enhancement of glutamater-gic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons.Additionally,skin stroking,an easier method to translate into clinical practice,activated the somatosensory cortex,thereby promoting OPC proliferation,remyelination and cognitive recovery following cerebral hypoperfusion.In summary,we demonstrated that activating glutamatergic neurons in the somatosen-sory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion.It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

Chronic cerebral hypoperfusionOptogenetic stimulationOligodendrocyte progenitor cellIschemic vascular dementiaGlutamatergic neuronRemyelination

Yi-Ting Zhou、Da-Dao An、Yi-Xin Xu、Ying Zhou、Qing-Qing Li、Hai-Bin Dai、Xiang-Nan Zhang、Yi Wang、Min Lou、Zhong Chen、Wei-Wei Hu

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Department of Pharmacology and Department of Pharmacy of the Second Affiliated Hospital,NHC and CAMS Key Laboratory of Medical Neurobiology,School of Basic Medical Sciences,College of Pharmaceutical Sciences,Zhejiang University School of Medicine,Hangzhou 310058,China

Department of Pharmacy,Sir Run Run Shaw Hospital,Hangzhou 310012,China

Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province,School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China

Department of Neurology,the Second Affiliated Hospital of Zhejiang University,School of Medicine,Hangzhou 310003,China

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国家自然科学基金国家自然科学基金国家重点研发计划浙江省自然科学基金浙江省自然科学基金

81973302819035802020YFA0803900LR17H310001LYY22H310003

2024

自然科学基础研究(英文)

自然科学基础研究(英文)

CSTPCD
ISSN:
年,卷(期):2024.(1)
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