Neuroplasticity, the aging brain, and Alzheimer's disease.
A variety of neurological disorders are associated with the loss of specific populations of neurons. Alzheimer's, Parkinson's, and Huntington's diseases present unique constellations of behavioral and neurological abnormalities which result from the degeneration of neurons in specific regions of the brain. Approaches to the treatment of these neurodegenerative disorders have met with either limited or no success. New treatment strategies based upon a better understanding of the inherent mechanisms of neuroplasticity might provide more rational approaches to prevent, limit, or treat these and other neurodegenerative disorders. The development and standardization of appropriate animal models of neurodegenerative disorders will be essential to realize this possibility. Using the cholinergic neurotoxin AF64A we have developed a rodent model of cholinergic hypofunction that exhibits behavioral, anatomical, and neurochemical deficits very analogous to those observed in Alzheimer's disease. Furthermore, we have found that administration of neurotrophic factors, such as ganglioside AGF2, and the transplantation of fetal cholinergic neurons into the hippocampus can attenuate both the behavioral and neurobiological alterations induced by AF64A. These efforts should lead to the development of innovative clinical strategies and they should also help to elucidate the neurobiology of brain injury and recovery of function.
Walsh
T J
TJ
Department of Psychology, Rutgers University, New Brunswick, New Jersey 08903.
Opello
K D
KD
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D001388:Aziridines / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D016380:Brain Tissue Transplantation / Q000502:physiology; D002794:Choline / Q000031:analogs & derivatives / Q000633:toxicity; D005732:Gangliosides / Q000502:physiology; D006801:Humans; D009414:Nerve Growth Factors / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*
D001388:Aziridines; D005732:Gangliosides; D009414:Nerve Growth Factors; C044894:ethylcholine aziridinium; D002794:Choline