Adaptor Protein LNK Is a Negative Regulator of Brain Neural Stem Cell Proliferation after Stroke.

Summary, in English

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.

• Author: 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
• Department/s: Neurology, Lund; Developmental and Regenerative Neurobiology; Stem Cell Center; Tumor microenvironment; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy; MultiPark: Multidisciplinary research focused on Parkinson´s disease
• Publishing year: 2012
• Language: English
• Pages: 5151-5164
• Publication/Series: The Journal of neuroscience : the official journal of the Society for Neuroscience
• Volume: 32
• Issue: 15
• Links: http://www.ncbi.nlm.nih.gov/pubmed/22496561?dopt=Abstract; http://dx.doi.org/10.1523/JNEUROSCI.0474-12.2012
• Document type: Journal article
• Publisher: Society for Neuroscience
• Topic: Neurosciences
• Status: Published
• Research group: Developmental and Regenerative Neurobiology
• ISBN/ISSN/Other: ISSN: 1529-2401