Carl W. Cotman
School of Medicine
Director, Institute for Brain Aging and Dementia, Research and Graduate Studies
PH.D., University of Indiana
Phone: (949) 824-5847
Fax: (949) 824-2071
University of California, Irvine
1113 Gillespie Building
Mail Code: 4540
Irvine, CA 92697
Amyloid, C1q, Alzheimer's disease, apoptosis, successful aging, dementia
The research of the Cotman laboratory is aimed toward understanding the mechanisms causing neuronal degeneration in Alzheimer’s disease (AD) and the development of interventions to promote successful aging. We have been investigating the possibility that the accumulation of risk factors in the aged brain such as beta-amyloid and oxidative damage activate pathways associated with apoptosis. As predicted from cell culture models, caspases and related pathways are up regulated and caspase cleavage products of proteins such fodrin; APP and tau accumulate in the AD brain. In the case of fodrin the accumulation parallels that of tangle formation, suggesting that like tangles this mechanism correlates with cognitive decline (Rohn, 2000).
In parallel, we have been investigating possible behavioral interventions that may aid the brain in aging successfully. We suggest that exercise and environmental enrichment can have beneficial effects on brain function and heath. Our findings show that Brain Derived Neurotrophic Factor (BDNF), a trophic factor known to support neuronal survival and plasticity, is induced with a few days of voluntary running in animal studies. In rodents and aged canines (dogs), current studies are investigating the mechanisms and functional consequences of this simple and widely practiced behavior (Cotman and Berchtold, 2002). We are finding that environmental enrichment particularly if combined with antioxidants can result in a slowing of rate of decline in learning and memory in the aged canine (Milgram, et al. in press). One of the current goals of our research is to evaluate such intervention strategies in elderly humans in collaboration with other investigators in the field. Specific training. Training is provided in basic cell culture biochemical methods as well as neuroanatomical methods applied to the study of the aging and AD brain. We also participate in the design and performance of clinical trials in collaboration with others. Collaborators include Kawas, Tenner, Glabe, and Sheu.
Berchtold, N.C. and Cotman, C.W. (2002). Exercise: A Behavioral Intervention to Enhance Brain Health and Plasticity, Trends in Neuroscience, Vol. 25 No. 6 June.
Cotman, C.W., Head, E., Muggenburg, B.A., Zicker, S., and Milgram, N.W., (2002). Brain Aging in the Canine: A Diet Enriched in Antioxidants Reduces Cognitive Dysfunction, Neurobiology of Aging, in press.
Berchtold, N.C., Kesslak, J.P., Pike, C.J., Adlard, P.A.,Berchtold, N.C., Kesslak, J.P., Pike, C.J., Adlard, P.A., and Cotman, C.W. (2001). Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus, European Journal of Neuroscience 14:1-13.
Tong, L., Thornton, P.L., Balazs, R., and Cotman, C.W. (2001). b-amyloid1-42 impairs activity-dependent CREB signaling in neurons at concentrations at which cell survival is not comprised, Journal of Biological Chemistry 276 (20): 17301-17306.