Search form

TitleThe aPKC-CBP Pathway Regulates Post-stroke Neurovascular Remodeling and Functional Recovery.
Publication TypeJournal Article
Year of Publication2017
AuthorsGouveia, Ayden, Matthew Seegobin, Timal S. Kannangara, Ling He, Fredric Wondisford, Cesar H. Comin, Luciano da F. Costa, Jean-Claude Béïque, Diane C. Lagace, Baptiste Lacoste, and Jing Wang
JournalStem Cell Reports
Volume9
Issue6
Pagination1735-1744
Date Published2017 12 12
ISSN2213-6711
KeywordsAnimals, Brain Ischemia, Cellular Reprogramming, CREB-Binding Protein, Mice, Neurogenesis, Pericytes, Phosphorylation, Protein Kinase C, Recovery of Function, Signal Transduction, Stroke, Stroke Rehabilitation, Vascular Remodeling
Abstract

Epigenetic modifications have emerged as attractive molecular substrates that integrate extrinsic changes into the determination of cell identity. Since stroke-related brain damage releases micro-environmental cues, we examined the role of a signaling-induced epigenetic pathway, an atypical protein kinase C (aPKC)-mediated phosphorylation of CREB-binding protein (CBP), in post-stroke neurovascular remodeling. Using a knockin mouse strain (CbpS436A) where the aPKC-CBP pathway was defective, we show that disruption of the aPKC-CBP pathway in a murine focal ischemic stroke model increases the reprogramming efficiency of ischemia-activated pericytes (i-pericytes) to neural precursors. As a consequence of enhanced cellular reprogramming, CbpS436A mice show an increased transient population of locally derived neural precursors after stroke, while displaying a reduced number of i-pericytes, impaired vascular remodeling, and perturbed motor recovery during the chronic phase of stroke. Together, this study elucidates the role of the aPKC-CBP pathway in modulating neurovascular remodeling and functional recovery following focal ischemic stroke.

DOI10.1016/j.stemcr.2017.10.021
Alternate JournalStem Cell Reports
PubMed ID29173896
PubMed Central IDPMC5785704
Grant ListR01 DK107641 / DK / NIDDK NIH HHS / United States
MOP378718 / / CIHR / Canada
MOP142420 / / CIHR / Canada