Neurodegeneration and chronic drug-induced changes in brain signaling pathways.
Stem Cells
Stem cells, which are found in specific brain regions and form new neurons,
could be involved in the regeneration of the brain during recovery from addiction.
Binge drinking reduces proliferation of neural progenitor cells in brain.
Gene Delivery
A third area of research involves the use of gene delivery to understand how alterations in genes alter brain function and behavior.
Research Synopsis:
Mental disease, including addiction and neurodegeneration, are central themes of the laboratory's research. Addiction has many components, one of which is long term changes in gene expression and structure in brain. Binge drinking-induced changes in specific brain regions are hypothesized to contribute to the progression to addiction. This could overlap with brain structure/function changes in other mental diseases, particularly depression. The mechanisms of binge drinking-induced brain damage are not clearly understood, but appear to involve oxidative changes in brain similar to aging and neurodegenerative disorders such as Alzheimer's disease. Alcoholics are known to have reduced brain mass which begins to grow back during recovery. The regeneration of brain cells is a new area that could be related to recovery from addiction. Three key areas are investigated using rat models: the mechanisms, characteristics and functional consequences of binge drinking-induced brain damage. Histochemical, neurochemical and gene induction studies investigate the changes in brain and associated behaviors found with binge drinking induced brain damage.
Recent Publications:
Crews, F.T., Buckley, T., Dodd, P.R., Ende, G., Fole,y N., Harpe,r C., and He, J. (2005) Alcoholic neurobiology: changes in dependence and recovery. Alcohol Clin Exp Res 29(8): 1504-13. Abstract
He, J., Nixon, K., Shetty, A.K., and Crews, F.T. (2005) Chronic alcohol exposure reduces hippocampal neurogenesis and dendritic growth of newborn neurons. Eur J Neurosci 21(10): 2711-20. Abstract
Monti, P.M., Miranda, R. Jr., Nixon, K., Sher, K.J., Swartzwelder, H.S., Tapert, S.F., White, A., and Crews, F.T. (2005) Adolescence: booze, brains, and behavior. Alcohol Clin Exp Res 29(2): 207-20. Abstract
Pandey, S.C., Chartoff, E.H., Carlezon, W.A. Jr., Zou, J., Zhang, H., Kreibich, A.S., Blendy, J.A., and Crews, F.T. (2005) CREB gene transcription factors: role in molecular mechanisms of alcohol and drug addiction. Alcohol Clin Exp Res29(2): 176-84. Abstract
Zou, J.Y., and Crews, F.T. (2005) TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition. Brain Res 1034(1-2): 11-24. Abstract
