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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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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]
Número total de Autores: 11
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
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: STEM CELL REPORTS; v. 9, n. 6, p. 1735-1744, DEC 2017.
Citações Web of Science: 5
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: 15/18942-8 - Associando redes complexas com espaços efetivos de atributos
Beneficiário:Cesar Henrique Comin
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 11/50761-2 - Modelos e métodos de e-Science para ciências da vida e agrárias
Beneficiário:Roberto Marcondes Cesar Junior
Linha de fomento: Auxílio à Pesquisa - Temático