Adaptor protein LNK is a negative regulator of brain neural stem cell proliferation after stroke

Henrik Ahlenius, Karthikeyan Devaraju, Emanuela Monni, Koichi Oki, Somsak Wattananit, Vladimer Darsalia, Robert E. Iosif, Olof Torper, James C. Wood, Sebastian Braun, Lucas Jagemann, Ulrike A. Nuber, Elisabet Englund, Sten Eirik W. Jacobsen, Olle Lindvall, Zaal Kokaia

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Ischemic stroke causes transient increase of neural stem and progenitor cell (NSPC) proliferation in the subventricular zone (SVZ), and migration of newly formed neuroblasts toward the damaged area where they mature to striatal neurons. The molecular mechanisms regulating this plastic response, probably involved in structural reorganization and functional recovery, are poorly understood. The adaptor protein LNK suppresses hematopoietic stem cell self-renewal, but its presence and role in the brain are poorly understood. Here wedemonstrate thatLNKis expressed in NSPCs in the adult mouse andhumanSVZ. LNK -/- mice exhibited increasedNSPCproliferation after stroke, but not in intact brain or following status epilepticus. Deletion of Lnk caused increased NSPC proliferation while overexpression decreased mitotic activity of these cells in vitro. We found that Lnk expression after stroke increased in SVZ through the transcription factors STAT1/3. LNK attenuated insulin-like growth factor 1 signaling by inhibition of AKT phosphorylation, resulting in reduced NSPC proliferation. Our findings identify LNK as a stroke-specific, endogenous negative regulator of NSPC proliferation, and suggest that LNK signaling is a novel mechanism influencing plastic responses in postischemic brain.

Original languageEnglish
Pages (from-to)5151-5164
Number of pages14
JournalJournal of Neuroscience
Issue number15
Publication statusPublished - 2012 Apr 11
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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