期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 23, 页码 5439-5444出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0974-04.2004
关键词
Alzheimer; differentiation; hippocampus; stem cells; neurogenesis; amyloid beta peptide
资金
- NIA NIH HHS [AG08702, P50 AG008702] Funding Source: Medline
- NINDS NIH HHS [NS-15076, R01 NS015076] Funding Source: Medline
The adult mammalian brain contains neural stem cells (NSCs) with self-renewal and multilineage potential in the hippocampus and subventricular zone. However, neurogenesis from these areas does not compensate for neuronal loss in age-related neurodegenerative disorders such as Alzheimer's disease (AD). To test whether an impairment of neurogenesis could contribute to the pathogenesis of AD, we examined the effects of amyloid-beta peptide (Abeta) on the survival and neuronal differentiation of cultured NSCs from striatum and hippocampus. We show that Abeta peptide does not impair the neurogenic rate in NSC progeny, but that it increases the total number of neurons in vitro in a dose-dependent manner. The neurogenic effect of Abeta peptide is not dependent on soluble factors released from the NSC progeny. Neurogenesis is induced by Abeta42 and not Abeta40 or Abeta25-35, and the activity appears to be a property of Abeta oligomers and not fibrils. These results suggest that Abeta may have positive as well as deleterious actions, and that a knowledge of the mechanisms involved in the former could be valuable in exploiting the regenerative and plastic potential of the brain in preventing and treating Alzheimer's disease.
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