Region-specific and activity-dependent regulation of SVZ neurogenesis and recovery after stroke.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
02 07 2019
Historique:
pubmed: 15 6 2019
medline: 31 3 2020
entrez: 15 6 2019
Statut: ppublish

Résumé

Stroke is the leading cause of adult disability. Neurogenesis after stroke is associated with repair; however, the mechanisms regulating poststroke neurogenesis and its functional effect remain unclear. Here, we investigate multiple mechanistic routes of induced neurogenesis in the poststroke brain, using both a forelimb overuse manipulation that models a clinical neurorehabilitation paradigm, as well as local manipulation of cellular activity in the peri-infarct cortex. Increased activity in the forelimb peri-infarct cortex via either modulation drives increased subventricular zone (SVZ) progenitor proliferation, migration, and neuronal maturation in peri-infarct cortex. This effect is sensitive to competition from neighboring brain regions. By using orthogonal tract tracing and rabies virus approaches in transgenic SVZ-lineage-tracing mice, SVZ-derived neurons synaptically integrate into the peri-infarct cortex; these effects are enhanced with forelimb overuse. Synaptic transmission from these newborn SVZ-derived neurons is critical for spontaneous recovery after stroke, as tetanus neurotoxin silencing specifically of the SVZ-derived neurons disrupts the formation of these synaptic connections and hinders functional recovery after stroke. SVZ-derived neurogenesis after stroke is activity-dependent, region-specific, and sensitive to modulation, and the synaptic connections formed by these newborn cells are functionally critical for poststroke recovery.

Identifiants

pubmed: 31196958
pii: 1811825116
doi: 10.1073/pnas.1811825116
pmc: PMC6612913
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

13621-13630

Informations de copyright

Copyright © 2019 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Huixuan Liang (H)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Handi Zhao (H)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Amy Gleichman (A)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Michal Machnicki (M)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Sagar Telang (S)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Sydney Tang (S)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Mary Rshtouni (M)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Jack Ruddell (J)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

S Thomas Carmichael (ST)

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 scarmichael@mednet.ucla.edu.

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Classifications MeSH