Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris water maze. However, alcohol did not alter the spontaneous locomotor activity which was determined by the open field test. GSK3β is a multi-function serine/threonine protein kinase regulating both neuronal survival and neurogenesis and plays an important role in various neurodegenerative disorders. We have previously shown that GSK3β is a key mediator of alcohol-induced neuron apoptosis in the developing brain. We showed here binge alcohol exposure caused GSK3β activation by inducing dephosphorylation at Ser9 without affecting the phosphorylation of Tyr216 in the hippocampus. Thus, GSK3β may be involved in binge alcohol exposure-induced neuronal damage to the adolescent hippocampus.
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This research was supported by the National Natural Science Foundation of China (31271142 and 31570921 to Z.J.), Shanghai Key Laboratory of Health Identification and Assessment (13DZ2261000), Shanghai Municipal Commission of Health and Family Planning (201540206 to Z.J.). J. Luo was supported by grants from NIH/NIAAA (AA017226 and AA015407).
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-21341-w.
Ji, Zhe; Yuan, Lin; Lu, Xiong; Ding, Hanqing; Luo, Jia; and Ke, Zun-Ji, "Binge Alcohol Exposure Causes Neurobehavioral Deficits and GSK3β Activation in the Hippocampus of Adolescent Rats" (2018). Pharmacology and Nutritional Sciences Faculty Publications. 67.
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