UMR1247 INSERM, Groupe de Recherche sur l'Alcool et les Pharmacodépendances, Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, Amiens, France.
Plateforme d'Ingénierie Cellulaire & Analyses des Protéines (ICAP), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, Amiens, France.
Alcohol Clin Exp Res. 2022 Feb;46(2):207-220. doi: 10.1111/acer.14757. Epub 2021 Dec 21.
Multiple ethanol binge drinking-like exposures during adolescence in the rat induce neuroinflammation, loss of neurogenesis, and cognitive deficits in adulthood. Interestingly, the first ethanol binge drinking-like exposure during adolescence also induces short- term impairments in cognition and synaptic plasticity in the hippocampus though the cellular mechanisms of these effects are unclear. Here, we sought to determine which of the cellular effects of ethanol might play a role in the disturbances in cognition and synaptic plasticity observed in the adolescent male rat after two binge-like ethanol exposures.
Using immunochemistry, we measured neurogenesis, neuronal loss, astrogliosis, neuroinflammation, and synaptogenesis in the hippocampus of adolescent rats 48 h after two binge-like ethanol exposures (3 g/kg, i.p., 9 h apart). We used flow cytometry to analyze activated microglia and identify the TLR4-expressing cell types.
We detected increased hippocampal doublecortin immunoreactivity in the subgranular zone (SGZ) of the dentate gyrus (DG), astrogliosis in the SGZ, and a reduced number of mature neurons in the DG and in CA3, suggesting compensatory neurogenesis. Synaptic density decreased in the stratum oriens of CA1 revealing structural plasticity. There was no change in microglial TLR4 expression or in the number of activated microglia, suggesting a lack of neuroinflammatory processes, although neuronal TLR4 was decreased in CA1 and DG.
Our findings demonstrate that the cognitive deficits associated with hippocampal synaptic plasticity alterations that we previously characterized 48 h after the first binge-like ethanol exposures are associated with hippocampal structural plasticity, astrogliosis, and decreased neuronal TLR4 expression, but not with microglia reactivity.
在大鼠青春期进行多次乙醇 binge 样暴露会导致神经炎症、神经发生丧失和成年期认知缺陷。有趣的是，青春期第一次乙醇 binge 样暴露也会导致短期认知和海马突触可塑性受损，尽管这些影响的细胞机制尚不清楚。在这里，我们试图确定乙醇的哪些细胞效应可能在青春期雄性大鼠两次 binge 样乙醇暴露后观察到的认知和突触可塑性紊乱中发挥作用。
使用免疫化学方法，我们测量了两次 binge 样乙醇暴露（3 g/kg，ip，间隔 9 小时）后 48 小时青春期大鼠海马中的神经发生、神经元丢失、星形胶质细胞增生、神经炎症和突触发生。我们使用流式细胞术分析激活的小胶质细胞并鉴定 TLR4 表达细胞类型。
我们在齿状回（DG）的颗粒下区（SGZ）检测到海马中双皮质素免疫反应性增加，SGZ 中星形胶质细胞增生，以及 DG 和 CA3 中成熟神经元数量减少，提示代偿性神经发生。CA1 中的层状或神经发生密度降低表明存在结构可塑性。小胶质细胞 TLR4 表达或激活小胶质细胞数量没有变化，提示没有神经炎症过程，尽管 CA1 和 DG 中的神经元 TLR4 减少。
我们的研究结果表明，我们之前在第一次 binge 样乙醇暴露后 48 小时描述的与海马突触可塑性改变相关的认知缺陷与海马结构可塑性、星形胶质细胞增生和神经元 TLR4 表达减少有关，而与小胶质细胞反应无关。
