Deutsch
 
Benutzerhandbuch Datenschutzhinweis Impressum Kontakt
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

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

MPG-Autoren
Es sind keine MPG-Autoren in der Publikation vorhanden
Externe Ressourcen
Es sind keine Externen Ressourcen verfügbar
Volltexte (frei zugänglich)

Devaraju_2012_adaptor.pdf
(Verlagsversion), 4MB

Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Ahlenius, H., Devaraju, K., Monni, E., Oki, K., Wattananit, S., Darsalia, V., et al. (2012). Adaptor Protein LNK Is a Negative Regulator of Brain Neural Stem Cell Proliferation after Stroke. The Journal of Neuroscience, 32(15), 5151-5164. doi:10.1523/JNEUROSCI.0474-12.2012.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002E-799F-6
Zusammenfassung
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.