S15-4 Neuroinflammation and epigenetic processes after only two binges of ethanol in young adults rats
Résumé
Adolescence is a developmental period during which binge drinking is common in humans while several cerebral structures achieve maturation. Several studies demonstrated that ethanol consumption including binge drinking behavior induces neuroinflammation. In preclinical studies, binge-like ethanol exposure typically includes 2 consecutive days of ethanol administration (3 g/kg dose, i.p. route), for one-two week(s) and with a 2 day interval between injections. However, we recently showed that only two of such ethanol “binges” in adolescent rats are sufficient to reversibly abolish long-term synaptic depression (LTD) in the hippocampus and to evoke cognitive deficits after a 48 h period of abstinence (Silvestre de Ferron et al., 2015). However, whether these functional consequences in the hippocampus are accompanied with neuroinflammation and/or epigenetic alterations have never been explored.
We performed immunohistochemistry of cellular markers for epigenetic processes, neuroinflammation, neurogenesis and synaptogenesis on hippocampus slices from adolescent rat (PND42) treated with 2 ethanol binges (3 g/kg, i.p, 8 hours apart) followed by a 48 h period of abstinence.
Forty eight hours after the 2 binges, vimentine and GFAP co-labelling was decreased in CA1 and increased in the Sub-Granular Zone (SGZ) of Dentate Gyrus (DG). Doublecortin was increased in SGZ whereas NeuN was decreased in the granular zone and in CA3. Synaptophysin was decreased in the stratum oriens of CA1. HMGB1 was unaltered in any area while TLR4 was increased in the hilus of DG and in CA3. Expression of acetylated Histone 4 (Ac-H4) was decreased in CA1 and DG areas, whereas expression of Ac-H3 was unchanged. Expression levels of HDAC2 was increased in CA1 only. Overall, reactive astrogliosis and new-generated neurons were present in DG accompanied with reduced synaptogenesis in CA1 area, and reduced numbers of neurons in DG and CA3, suggesting a compensatory neurogenesis and morphologic plasticity 48 h after 2 binges.
In conclusion, only two binges are sufficient to induce neuronal injury and to alter morphologic plasticity in the hippocampus via modification of epigenetic processes, neurogenesis, synaptogenesis and astrogliosis. We suggest these alterations may reflect the abolition of LTD and the accompanying memory deficit we previously reported.