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

Ahlenius, Henrik LU ; Devaraju, Karthikeyan LU ; Monni, Emanuela LU ; Oki, Koichi LU ; Wattananit, Somsak LU ; Darsalia, Vladimer; Iosif, Robert; Torper, Olof LU ; Wood, James LU and Braun, Sebastian LU , et al. (2012) In The Journal of neuroscience : the official journal of the Society for Neuroscience 32(15). p.5151-5164
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... (More)
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. (Less)
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published
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The Journal of neuroscience : the official journal of the Society for Neuroscience
volume
32
issue
15
pages
5151 - 5164
publisher
Society for Neuroscience
external identifiers
  • wos:000302793500014
  • pmid:22496561
  • scopus:84859520686
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0474-12.2012
language
English
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yes
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f1f365a4-78fe-495b-b757-eb16098af283 (old id 2519520)
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http://www.ncbi.nlm.nih.gov/pubmed/22496561?dopt=Abstract
date added to LUP
2012-05-06 16:43:21
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2017-01-01 07:43:50
@article{f1f365a4-78fe-495b-b757-eb16098af283,
  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.},
  author       = {Ahlenius, Henrik and Devaraju, Karthikeyan and Monni, Emanuela and Oki, Koichi and Wattananit, Somsak and Darsalia, Vladimer and Iosif, Robert and Torper, Olof and Wood, James and Braun, Sebastian and Jagemann, Lucas and Nuber, Ulrike and Englund, Elisabet and Jacobsen, Sten Eirik W and Lindvall, Olle and Kokaia, Zaal},
  issn         = {1529-2401},
  language     = {eng},
  number       = {15},
  pages        = {5151--5164},
  publisher    = {Society for Neuroscience},
  series       = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  title        = {Adaptor Protein LNK Is a Negative Regulator of Brain Neural Stem Cell Proliferation after Stroke.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.0474-12.2012},
  volume       = {32},
  year         = {2012},
}