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

Ayden Gouveia, Matthew Seegobin, Timal S. Kannangara, Ling He, Fredric Wondisford, Cesar H. Comin (ORCID), Luciano Da F. Costa, Jean-Claude Béïque, Diane C. Lagace, Baptiste Lacoste, Jing Wang

Stem Cell Reports, 9(6): 1735-1744. . DOI: 10.1016/j.stemcr.2017.10.021.

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.

Citation

@article{Gouveia2017The,
  title   = {The aPKC-CBP Pathway Regulates Post-stroke Neurovascular Remodeling and Functional Recovery},
  author  = {Gouveia, Ayden and Seegobin, Matthew and Kannangara, Timal S. and He, Ling and Wondisford, Fredric and Comin, Cesar H. and Costa, Luciano Da F. and Béïque, Jean-Claude and Lagace, Diane C. and Lacoste, Baptiste and Wang, Jing},
  journal = {Stem Cell Reports},
  year    = {2017},
  volume  = {9},
  number  = {6},
  pages   = {1735--1744},
  doi     = {10.1016/j.stemcr.2017.10.021}
}