P.6.a.006 Alcohol pharmacokinetics in Korean healthy females

At the end of this procedure, a series of behavioural analyses, including novel object recognition and fear conditioning tests, were conducted in ethanol and water mice. In another series of ethanol and water mice, long term potentiation (LTP) on hippocampal slices was measured by recording synaptic responses of CA1 pyramidal neurons elicited by stimulation of the Schaffer collateral/commissural pathway. Finally, mouse brains from both ethanol and water groups were dissected to performed western blotting and methylated DNA immunoprecipitation (MeDIP) studies. Data were analyzed using Student’s t test, one-way or two-way analyses of variance. Results: A three week chronic and moderate ethanol consumption significantly reduced the DNA methylation of the different CpG islands within Bdnf gene in both the CA1 and CA3 subfields of the hippocampus, further demonstrating a chromatin remodelling effect of ethanol at plasticity gene level, in line with in the promoting effect of ethanol on hippocampal neurogenesis in C57BL/6J mice [3]. Ethanol also significantly augmented the phosphorylation of ERK, AKT and CREB proteins which belong to the BDNF signalling pathway. Conversely, learning and memory capacities were altered in both the novel object recognition and the fear conditioning tests suggesting the impairment in hippocampus-dependent memory. However, in the present condition of consumption, ethanol had no effects on the LTP recorded in the CA1 region of hippocampal slices. Conclusion: All together, these data provided supplementary evidences that the stimulating effect of ethanol on hippocampal BDNF expression could be due, in part, to a chromatin remodelling at the level of the Bdnf gene. High BDNF expression can in turn impact its signalling pathway efficiency, as shown by the high level of ERK, AKT and CREB phosphorylation in ethanol mice. However, ethanol was also showed to damp hippocampusdependent learning and memory capacities but without modifying synaptic plasticity. Whether the effects of ethanol on neuroplasticity and learning are unconnected or whether the increase in neuroplasticity observed in mice having consumed ethanol for 3 weeks could be an adaptive response to ethanol-induced learning deficits are questions to be addressed in future studies.