The aPKC-CBP Pathway Regulates Post-stroke Neurovascular Remodeling and Functional Recovery.
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.
['Gouveia|Ayden|A|', 'Seegobin|Matthew|M|', 'Kannangara|Timal S|TS|', 'He|Ling|L|', 'Wondisford|Fredric|F|', 'Comin|Cesar H|CH|', 'Costa|Luciano da F|LDF|', 'Béïque|Jean-Claude|JC|', 'Lagace|Diane C|DC|', 'Lacoste|Baptiste|B|', 'Wang|Jing|J|']
D000818:Animals D002545:Brain Ischemia D050882:CREB-Binding Protein D065150:Cellular Reprogramming D051379:Mice D055495:Neurogenesis D020286:Pericytes D010766:Phosphorylation D011493:Protein Kinase C D020127:Recovery of Function D015398:Signal Transduction D020521:Stroke D000071939:Stroke Rehabilitation D066253:Vascular Remodeling
aPKC-CBP pathway ischemic stroke pericyte neural precursors cellular reprogramming vascular remodeling