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 is 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. Recent studies have suggested that neuroinflammation may contribute to degeneration and loss of neurogenesis during binge drinking. In contrast to the degeneration found during binge drinking there is a regeneration of brain cells during abstinence 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. Current studies suggest that neuroinflammation contributes to degeneration and loss of neurogenesis, whereas regeneration during abstinence-recovery is related to increased neurogenesis.
A second area of research interest involves stem cells, which are found in specific brain regions and form new neurons. These stem cells could be involved in the regeneration of the brain during recovery from addiction. Binge drinking reduces proliferation of neural progenitor cells in brain.
A third area of research involves the use of gene delivery to understand how alterations in genes alter brain function and behavior.
Center Line Articles
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Crews F, Nixon K, Kim D, Joseph J, Shukitt-Hale B, Qin L, Zou J. BHT blocks NF-kappaB activation and ethanol-induced brain damage. Alcohol Clin Exp Res. 2006 Nov;30(11):1938-49.
Nicholas PC, Kim D, Crews FT, Macdonald JM. Proton nuclear magnetic resonance spectroscopic determination of ethanol-induced formation of ethyl glucuronide in liver.
Anal Biochem. 2006 Nov 15;358(2):185-91.
Zou, J, Crews, F. CREB and NF-kappaB Transcription Factors Regulate Sensitivity to Excitotoxic and Oxidative Stress Induced Neuronal Cell Death. Cell Mol Neurobiol. 2006 Jul;26(4-6):383-403.
Crews FT, Bechara R, Brown LA, Guidot DM, Mandrekar P, Oak S, Qin L, Szabo G, Wheeler M, Zou J. Cytokines and alcohol. Alcohol Clin Exp Res. 2006 Apr; 30 (4): 720-30.
Crews FT, Mdzinarishvili A, Kim D, He J, Nixon K. Neurogenesis in adolescent brain is potently inhibited by ethanol. Neuroscience. 2006;137(2):437-45.
Crews FT, Buckley T, Dodd PR, Ende G, Foley N, Harper C, He J, Innes D, Loh el-W, Pfefferbaum A, Zou J, Sullivan EV. Alcoholic neurobiology: changes in dependence and recovery. Alcohol Clin Exp Res. 2005 Aug;29(8):1504-13.
He J, Nixon K, Shetty AK, Crews FT. Chronic alcohol exposure reduces hippocampal neurogenesis and dendritic growth of newborn neurons. Eur J Neurosci. 2005 May;21(10):2711-20.
Monti PM, Miranda R Jr, Nixon K, Sher KJ, Swartzwelder HS, Tapert SF, White A, Crews FT. Adolescence: Booze, Brains, and Behavior. Alcohol Clin Exp Res. 2005 Feb;29(2):207-220.
Pandey SC, Chartoff EH, Carlezon WA Jr, Zou J, Zhang H, Kreibich AS, Blendy JA, Crews FT. CREB Gene Transcription Factors: Role in Molecular Mechanisms of Alcohol and Drug Addiction. Alcohol Clin Exp Res. 2005 Feb;29(2):176-184.