UMR1247 INSERM, Groupe de Recherche Sur L'Alcool Et Les Pharmacodépendances, Université de Picardie Jules Verne, Centre Universitaire de Recherche en Santé, Chemin du Thil, 80025, Amiens, France.
Psychopharmacology (Berl). 2022 Jul;239(7):2245-2262. doi: 10.1007/s00213-022-06112-w. Epub 2022 Mar 21.
Binge drinking during adolescence impairs learning and memory on the long term, and many studies suggest a role of neuroinflammation. However, whether neuroinflammation occurs after the very first exposures to alcohol remains unclear, while initial alcohol exposure impairs learning for several days in male rats.
To investigate the role of neuroinflammation in the effects of only two binge-like episodes on learning and on neuronal plasticity in adolescent male rat hippocampus.
Animals received two ethanol i.p. injections (3 g/kg) 9 h apart. Forty-eight hours later, we recorded long-term depression (LTD) and potentiation (LTP) in CA1 area of hippocampus slices. In isolated CA1, we measured immunolabelings for microglial activation and Toll-like receptor 4 (TLR4) and mRNA levels for several cytokines.
Forty-eight hours after the two binges, rats performed worse than control rats in novel object recognition, LTD was reduced, LTP was increased, and excitatory neurotransmission was more sensitive to an antagonist of the GluN2B subunit of the NMDA receptor. Exposure to ethanol with minocycline or indomethacin, two anti-inflammatory drugs, or with a TLR4 antagonist, prevented all effects of ethanol. Immunolabelings at 48 h showed a reduction of neuronal TLR4 that was prevented by minocycline pretreatment, while microglial reactivity was undetected and inflammatory cytokines mRNA levels were unchanged.
Two binge-like ethanol exposures during adolescence in rat involved neuroinflammation leading to changes in TLR4 expression and in GluN2B functioning inducing disturbances in synaptic plasticity and cognitive deficits. Anti-inflammatory drugs are good candidates to prevent brain function and memory deficits induced by few binge-drinking episodes.
青少年时期的狂饮会对长期的学习和记忆造成损害，许多研究表明这与神经炎症有关。然而，在首次接触酒精后是否会发生神经炎症尚不清楚，而最初的酒精暴露会使雄性大鼠的学习能力受损数天。
研究神经炎症在仅两次类似狂欢的酒精暴露对学习和青春期雄性大鼠海马神经元可塑性的影响中的作用。
动物接受两次腹腔注射乙醇（3g/kg），间隔 9 小时。48 小时后，我们在海马 CA1 区记录长时程抑制（LTD）和长时程增强（LTP）。在离体 CA1 区，我们测量了小胶质细胞激活和 Toll 样受体 4（TLR4）的免疫标记物以及几种细胞因子的 mRNA 水平。
在两次狂欢后 48 小时，与对照组大鼠相比，大鼠在新物体识别任务中表现较差，LTD 减少，LTP 增加，兴奋性神经传递对 NMDA 受体 GluN2B 亚基拮抗剂更敏感。用米诺环素或吲哚美辛（两种抗炎药物）或 TLR4 拮抗剂暴露于乙醇可预防乙醇的所有作用。48 小时的免疫标记显示神经元 TLR4 减少，米诺环素预处理可预防这种减少，而小胶质细胞反应未被检测到，炎性细胞因子 mRNA 水平没有改变。
在大鼠青春期进行两次类似狂欢的乙醇暴露会导致神经炎症，从而改变 TLR4 表达和 GluN2B 功能，导致突触可塑性紊乱和认知缺陷。抗炎药物是预防少量狂欢性饮酒引起的大脑功能和记忆缺陷的良好候选药物。
