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首页> 外文期刊>Addiction biology >Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A GluN2A / GluN2B NMDA GluN2B NMDA receptor subunits imbalance through HDAC2 HDAC2
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Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A GluN2A / GluN2B NMDA GluN2B NMDA receptor subunits imbalance through HDAC2 HDAC2

机译：青少年大鼠海马狂犬病饮用后的记忆和可塑性障碍：GLUN2A GLUN2A / GLUN2B NMDA GLUN2B NMDA受体亚单位通过HDAC2 HDAC2进行不平衡

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Abstract Ethanol (EtOH) induces cognitive impairment through modulation of synaptic plasticity notably in the hippocampus. The cellular mechanism(s) of these EtOH effects may range from synaptic signaling modulation to alterations of the epigenome. Previously, we reported that two binge‐like exposures to EtOH (3?g/kg, ip, 9?h apart) in adolescent rats abolished long‐term synaptic depression (LTD) in hippocampus slices, induced learning deficits, and increased N ‐methyl‐ d ‐aspartate (NMDA) receptor signaling through its GluN2B subunit after 48?hours. Here, we tested the hypothesis of EtOH‐induced epigenetic alterations leading to modulation of GluN2B and GluN2A NMDA receptor subunits. Forty‐two days old rats were treated with EtOH or the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB, 600?mg/kg, ip) injected alone or 30?minutes before EtOH. After 48?hours, learning was tested with novel object recognition while synaptic plasticity and the role of GluN2A and GluN2B subunits in NMDA‐fEPSP were measured in CA1 field of hippocampus slices. LTD and memory were impaired 48?hours after EtOH and NMDA‐fEPSP analysis unraveled changes in the GluN2A/GluN2B balance. These results were associated with an increase in histone deacetylase (HDAC) activity and HDAC2 mRNA and protein while Ac‐H4K12 labelling was decreased. EtOH increases expression of HDAC2 and mRNA level for GluN2B subunit (but not GluN2A), while HDAC2 modulates the promoter of the gene encoding GluN2B. Interestingly, NaB pretreatment prevented all the cellular and memory‐impairing effects of EtOH. In conclusion, the memory‐impairing effects of two binge‐like EtOH exposure involve NMDA receptor‐dependent LTD deficits due to a GluN2A/GluN2B imbalance resulting from changes in GluN2B expression induced by HDAC2.
机译：摘要乙醇（EtoH）通过显着调节海马突触可塑性诱导认知障碍。这些EtOH效应的细胞机制可以从突触信号调制范围到外形内蛋白组的改变。以前，我们报道了在青少年大鼠的eTOH（3？g / kg，IP，9μl，9μl）的两个静脉曝光废除了海马切片的长期突触凹陷（Ltd），诱导的学习缺陷，增加了n - 甲基-D-海地酸盐（NMDA）受体通过其GLUN2B亚基在48℃以下的时间信号传导。在这里，我们测试了EtOH诱导的表观遗传改变的假设，导致GLUN2B和GLUN2A NMDA受体亚基的调节。用EtOH或组蛋白脱乙酰酶抑制剂（HDACI）丁酸钠（NAB，600→Mg / kg，IP）用EtOH或组蛋白的脱乙酰酶抑制剂（Nab，600〜Mg / kg，IP）进行处理，或者在EtOH之前进行30℃。 48小时后，用新的对象识别进行学习，而在海马切片的CA1场中测量了NMDA-FEPSP中的GLUN2A和GLUN2B亚基的突触可塑性和GLUN2B亚基的作用。有限公司和记忆损害48？ETOH和NMDA-FEPSP分析GLUN2A / GLUN2B平衡的衰脱后的时间。这些结果与组蛋白脱乙酰酶（HDAC）活性和HDAC2 mRNA和蛋白质的增加有关，而AC-H4K12标记降低。 EtOH增加了GLUN2B亚基的HDAC2和mRNA水平的表达（但不是GLUN2A），而HDAC2调节编码GLUN2B的基因的启动子。有趣的是，NAB预处理阻止了EtOH的所有细胞和记忆损害。总之，两个静脉样EtOH暴露的记忆损伤效应涉及由于HDAC2诱导的GLUN2B表达的变化导致的GLUN2A / GLUN2B不平衡导致NMDA受体依赖性LTD。

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