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 Iosif, Olof Torper, James Wood, Sebastian Braun, Lucas Jagemann, Ulrike Nuber, Elisabet Englund, Sten Eirik W Jacobsen, Olle Lindvall, Zaal Kokaia

Research output: Contribution to journalArticlepeer-review

8 Citations (SciVal)

Abstract

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 we demonstrate that LNK is expressed in NSPCs in the adult mouse and human SVZ. Lnk(-/-) mice exhibited increased NSPC proliferation 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
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume32
Issue number15
DOIs
Publication statusPublished - 2012

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Neurology, Lund (013027000), Pathology, (Lund) (013030000), Stem Cell Center (013041110), Developmental Neurobiology (013210001)

Subject classification (UKÄ)

  • Neurosciences

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