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

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Abstract

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however 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 oligodendrocyte 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 glutamatergic 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 somatosensory 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.

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Most cited references 33

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Author and article information

Contributors

Wei-Wei Hu

Journal

Journal ID (nlm-ta): Fundam Res

Journal ID (iso-abbrev): Fundam Res

Title: Fundamental Research

Publisher: KeAi Publishing

ISSN (Print): 2096-9457

ISSN (Electronic): 2667-3258

Publication date PMC-release: 23 August 2022

Publication date Collection: January 2024

Publication date (Electronic): 23 August 2022

Volume: 4

Issue: 1

Pages: 188-198

Affiliations

[a ]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

[b ]Department of Pharmacy, Sir Run Run Shaw Hospital, Hangzhou 310012, China

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

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

Author notes

[* ]Corresponding author. huww@ 123456zju.edu.cn

[1]

These authors contributed equally to this work.

Article

Publisher Item ID: S2667-3258(22)00348-X

DOI: 10.1016/j.fmre.2022.08.007

PMC ID: 11197523

PubMed ID: 38933843

SO-VID: 94f8ed4d-871a-4d09-a1fd-9208bd291b6b

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 5 March 2022

Date revision received : 28 July 2022

Date accepted : 3 August 2022

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