The aPKC-CBP Pathway Regulates Post-stroke Neurovascular Remodeling and Functional Recovery

Autor(es):Mostrar menos -

Gouveia, Ayden ^{[1, 2]} ; Seegobin, Matthew ^[2] ; Kannangara, Timal S. ^{[1, 3]} ; He, Ling ^[4] ; Wondisford, Fredric ^[5] ; Comin, Cesar H. ^[6] ; Costa, Luciano da F. ^[7] ; Beique, Jean-Claude ^{[1, 8, 9, 3]} ; Lagace, Diane C. ^{[1, 8, 9, 3]} ; Lacoste, Baptiste ^{[1, 8, 9, 3]} ; Wang, Jing ^{[1, 8, 3, 2]}

Afiliação do(s) autor(es)

^[1] Univ Ottawa, Dept Cellular & Mol Med, Fac Med, Ottawa, ON - Canada

^[2] Ottawa Hosp, Regenerat Med Program, Res Inst, Ottawa, ON K1H 8L6 - Canada

^[3] Canadian Partnership Stroke Recovery, Ottawa, ON - Canada

^[4] Johns Hopkins Med Sch, Dept Pediat & Med, Baltimore, MD - USA

^[5] Rutgers Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ - USA

^[6] Univ Fed Sao Carlos, Dept Comp Sci, Sao Carlos, SP - Brazil

^[7] Univ Sao Paulo, Sao Carlos Inst Phys, POB 369, BR-13560970 Sao Carlos, SP - Brazil

^[8] Univ Ottawa, Brain & Mind Res Inst, Ottawa, ON - Canada

^[9] Ottawa Hosp, Neurosci Program, Res Inst, Ottawa, ON - Canada

• Tipo de documento: Artigo Científico
• Fonte: STEM CELL REPORTS; v. 9, n. 6, p. 1735-1744, DEC 2017.
• Citações Web of Science: 9

Resumo

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. (AU)

• Processo FAPESP: 11/50761-2 - Modelos e métodos de e-Science para ciências da vida e agrárias
• Beneficiário: Roberto Marcondes Cesar Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/18942-8 - Associando Redes Complexas com Espaços Efetivos de Atributos
• Beneficiário: Cesar Henrique Comin
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado