Optogenetic activation of glutamatergic neu⁃rons in somatosensory cortex promotes remy⁃elination in ischemic vascular dementia  

作　　者：ZHOU Yi-ting AN Da-dao XU Yi-xin ZHOU Ying LI Qing-qing ZHANG Xiang-nan WANG Yi LOU Min CHEN Zhong HU Wei-wei 

机构地区：[1]Department of Pharmacology and Department of Pharmacy of the Second Affiliated Hospital,NHC and CAMS Key Laboratory of Medical Neuro-biology,School of Basic Medical Sciences,Col-lege of Pharmaceutical Sciences,Zhejiang Univer-sity,Hangzhou 310012,China [2]Department of Pharmacy,Sir Run Run Shaw Hospital,Hangzhou 310020,China [3]Key Laboratory of Neurophar-macology and Translational Medicine of Zhejiang Province,School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China [4]Department of Neurology,the Second Affiliated Hospital of Zhejiang University,School of Medicine,Hangzhou 310003,China

出　　处：《中国药理学与毒理学杂志》2021年第9期696-697,共2页Chinese Journal of Pharmacology and Toxicology

摘　　要：OBJECTIVE Chronic cerebral hy⁃poperfusion can lead to progressive demyelin⁃ation and ischemic vascular dementia,yet there are no effective treatments.METHODS Magnetic resonance imaging was employed in patients with white matter damage,and optogenetics and skin stroking were exerted to activate glutamater⁃gic neurons in the somatosensory cortex in a clas⁃sical mouse model of ischemia vascular dementia.RESULTS White matter damage was correlated with disrupted cortical structure from MRI results.In a mouse model,activating glutamatergic neu⁃rons in the somatosensory cortex promotes prolif⁃eration of OPCs and remyelination to rescue cog⁃nitive impairment after chronic cerebral hypoper⁃fusion.Such therapeutic action was limited to stimulation with moderate intensity at the upper layers of the cortex,but was achieved over a wide time window after ischemia.Mechanistically,enhanced glutamatergic neuron-OPC functional synaptic connections are required for protection from activation of cortical glutamatergic neurons.Finally,skin stroking activation of the somatosen⁃sory cortex,an easier approach for clinical trans⁃lation,promoted OPC proliferation and remyelin⁃ation as well as cognitive recovery after cerebral hypoperfusion.CONCLUSION Activation of gluta⁃matergic neurons in the somatosensory cortex may serve as novel approaches for treating isch⁃emic vascular dementia through precise modula⁃tion of glutamatergic neuron-OPC circuits.

关 键 词：OPTOGENETICS glutamatergic neurons ischemic vascular dementia 

分 类 号：R749.1[医药卫生—神经病学与精神病学]