Journal
NEUROBIOLOGY OF DISEASE
Volume 29, Issue 2, Pages 316-326Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2007.09.005
Keywords
Alzheimer's disease; adult neurogenesis; neuronal loss; presenilin 1; neurodegeneration; conditional knockout; mice
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Funding
- NIA NIH HHS [R01 AG027854-01A1, AG027854, R01 AG027854, R01 AG040185] Funding Source: Medline
- NIMH NIH HHS [MH066243, R01 MH066243-02, R01 MH066243-04, R01 MH066243-01A1, R01 MH066243-03, R01 MH066243-05, R01 MH066243] Funding Source: Medline
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Alzheimer's disease (AD) is predominantly characterized by progressive neuronal loss in the brain. It has been recently found that adult neurogenesis in the hippocampal dentate gyrus of AD patients is significantly enhanced, while its functional significance is still unknown. By using an AD-like neurodegeneration mouse model, we show here that neurogenesis in the dentate gyrus was neurodegenerative stage-dependent. At early stages of neurodegeneration, neurogenesis was significantly enhanced and newly generated neurons migrated into the local neuronal network. Up to late stages of neurodegeneration, however, the survival of newly generated neurons was impaired so that the enhanced neurogenesis could not be detected anymore. Most interestingly, these dynamic changes in neurogenesis were correlated with the severity of neuronal loss in the dentate gyros, indicating that neurogenesis may work as a self-repairing mechanism to compensate for neurodegeneration. Therefore, to enhance endogenous neurogenesis at early stages of neurodegeneration may be a valuable strategy to delay neurodegenerative progress. (C) 2007 Elsevier Inc. All rights reserved.
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