Adult neurogenesis is functionally associated with AD-like neurodegeneration.
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 gyrus, 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.
Chen
Qian
Q
Department of Psychiatry, The University of Chicago, USA.
Nakajima
Akira
A
Choi
Se Hoon
SH
Xiong
Xiaoli
X
Sisodia
Sangram S
SS
Tang
Ya-Ping
YP
D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D053764:Presenilin-1 / Q000172:deficiency; D053766:Presenilin-2 / Q000172:deficiency
D009419:Nerve Tissue Proteins; D053764:Presenilin-1; D053766:Presenilin-2; D001973:Bromodeoxyuridine