Cognition Enhancement Research
Deficits in intellectual function are comorbid with many mental illnesses and neurological disorders. Mental retardation, autism, attention deficit disorder, schizophrenia, and depression all have cognitive components, as do Alzheimer ’s, Parkinson’s, Huntington’s, and other neurodegenerative diseases. Furthermore cognitive decline and memory impairment accompanies age-related changes in the brain and can indicate the onset of dementia. Cognitive enhancement is viewed as a strategy to treat these diseases, or to slow the effects of aging on brain function.
Cognition is mediated by changes in the biochemical constituency of synaptic machinery. We are characterizing signaling component of this machinery that underlie memory consolidation. We are particularly interested in the coordinated regulation of ionotropic glutamate receptors such as NMDA receptors and their synergy with cAMP signaling during synaptic remodeling and the consolidation of memory. The use of conditional knockout mice, viral gene transfer, neurophysiology and behavioral studies, and the development of small drug like peptides that interfere with protein interactions is providing insight into the processes underlying learning and new approaches for the development of selective and specific therapeutics to improve cognition.
See the following publication to learn more about our drug addiction research:
Drerup, J.M., Hayashi, K, Cui, H., Mettlach, G.L., Long, M.A., Marvin, M., Sun, X., Goldberg, M.S., Lutter, M. Bibb, J.A. (2010) Attention-Deficit/Hyperactivity-like phenotype in mice lacking the cyclin-dependent kinase 5 cofactor p35, Jour. of Biol. Psych. 68:1163-71 Dec. 15, 2010 issue cover photo.
Bibb, J.A., Mayford, M.R., Tsien, J.Z., Alberini, C.M. (2010) Cognition Enhancement Strategies, J. Neurosci. 30:14987-92.
Hawasli, A., Koovakkattu, D., Hayashi, K., Powell, C.M., Sinton, C., Bibb, J.A., and Cooper, D,.C. (2009) Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5, PLOSOne, 4:e5808.
Hawasli, A.H. and Bibb, J.A. (2007) Alternative roles for Cdk5 in learning and synaptic plasticity. Journal of Biotechnology, 2:941-948.
Hawasli, A.H., Benavides, D.R., Nguyen, C., Kansy, J.W., Chambon, P, Greengard, P., Powell, C.M., Cooper, D.C., and Bibb, J.A. (2007) Cdk5 governs learning, memory and synaptic plasticity via control of NMDA receptor degradation. Nature Neuroscience10:880-886.
Nguyen, C., Kansy, J. W., Fernandez, J., Gillardon, F., Allen, P.B., Hemmings, H.C., Jr., Nairn, A.C., and Bibb, J.A. (2007) Regulation of protein phosphatase inhibitor-1 by Cyclin-dependent kinase 5. J. Biol. Chem. 282:16511-16520.
Sahin, B., Shu, H., Fernandez, J., Nairn, A.C., Molkentin, J.D., and Bibb, J.A. (2006) Dual phosphorylation of inhibitor-1 by PKC and Cdk5 regulates its conversion of an inhibitor of PP-1 by PKA in the striatum. J. Biol. Chem. 281: 24322-24335.
Wei, F.-Y., Tomizawa, K., Ohshima, T., Asada, A., Nguyen, C., Bibb, J.A., Ishiguro, K., Saito, T., Kulkarni, A.B., Pant H.C., Mikoshiba, K., Matsui, H., and S. Hisanaga (2005) Control of Cdk5 activity by glutamatergic regulation of p35 stability. J. Neurochem.93: 502-512.
Ohshima, T., Ogura H., Tomizawa, K., Hayashi, K., Saito, T., Kamei, H., Bibb, J.A., Hisanaga, S., Matsui, H. and K. Mikoshiba (2005) Defective learning and memory in p35-deficient mice. J. Neurochem. 94: 917-925.