TY - JOUR
T1 - Neural stem cells improve memory in an inducible mouse model of neuronal loss
AU - Yamasaki, Tritia R.
AU - Blurton-Jones, Mathew
AU - Morrissette, Debbi A.
AU - Kitazawa, Masashi
AU - Oddo, Salvatore
AU - LaFerla, Frank M.
PY - 2007/10/31
Y1 - 2007/10/31
N2 - Neuronal loss is a major pathological outcome of many common neurological disorders, including ischemia, traumatic brain injury, and Alzheimer disease. Stem cell-based approaches have received considerable attention as a potential means of treatment, although it remains to be determined whether stem cells can ameliorate memory dysfunction, a devastating component of these disorders. We generated a transgenic mouse model in which the tetracycline-off system is used to regulate expression of diphtheria toxin A chain. After induction, we find progressive neuronal loss primarily within the hippocampus, leading to specific impairments in memory. We find that neural stem cells transplanted into the brain after neuronal ablation survive, migrate, differentiate and, most significantly, improve memory. These results show that stem cells may have therapeutic value in diseases and conditions that result in memory loss.
AB - Neuronal loss is a major pathological outcome of many common neurological disorders, including ischemia, traumatic brain injury, and Alzheimer disease. Stem cell-based approaches have received considerable attention as a potential means of treatment, although it remains to be determined whether stem cells can ameliorate memory dysfunction, a devastating component of these disorders. We generated a transgenic mouse model in which the tetracycline-off system is used to regulate expression of diphtheria toxin A chain. After induction, we find progressive neuronal loss primarily within the hippocampus, leading to specific impairments in memory. We find that neural stem cells transplanted into the brain after neuronal ablation survive, migrate, differentiate and, most significantly, improve memory. These results show that stem cells may have therapeutic value in diseases and conditions that result in memory loss.
KW - Ablation
KW - Functional recovery
KW - Memory
KW - Neuronal death
KW - Stem cells
KW - Transgenic
UR - http://www.scopus.com/inward/record.url?scp=35948979698&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35948979698&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1627-07.2007
DO - 10.1523/JNEUROSCI.1627-07.2007
M3 - Article
C2 - 17978032
AN - SCOPUS:35948979698
SN - 0270-6474
VL - 27
SP - 11925
EP - 11933
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 44
ER -