BACKGROUND/AIMS Ethanol (EtOH) exposure during a period comparable to the third trimester in human results in obvious neurotoxicity in the developing hippocampus and persistent deficits in hippocampal neurogenesis. Dexmedetomidine (DEX), a highly selective α-2-adrenergic agonist has been demonstrated to restore the impaired neurogenesis and neuronal plasticity in the dentate gyrus (DG) that follows neurological insult. However, the protective roles of DEX in the EtOH-induced deficits of postnatal neurogenesis in the hippocampus are still unknown. METHODS Mice were pretreated with DEX prior to EtOH exposure to determine its protective effects on impaired postnatal hippocampal neurogenesis. Six-day-old neonatal mice were treated with DEX (125 μg/kg) or saline, followed by EtOH at a total of 5 g/kg or an equivalent volume of saline on P7. Immunohistochemistry and immunofluorescence were used to evaluate the neurogenesis and activated microglia in the DG. Quantitative real time PCR (qRT-PCR) was utilized to assess the expression of inflammatory factors in the hippocampus. RESULTS DEX pretreatment attenuated the inhibition of EtOH-mediated hippocampal neurogenesis and the reduction of hippocampal neural precursor cells (NPCs). We further confirmed that DEX pretreatment reversed the EtOH-induced microglia activation in the DG as well as the upregulation of the hippocampal TNFα, MCP-1, IL-6, and IL-1β mRNA levels. CONCLUSION Our findings indicate that DEX pretreatment protects against EtOH-mediated inhibition of hippocampal neurogenesis in postnatal mice and reverses EtOH-induced neuroinflammation via repressing microglia activation and the expression of inflammatory cytokines.

中文翻译：

---

右美托咪定减弱了乙醇对新生小鼠海马神经发生的抑制作用。

背景/目的在与人的晚期三个月相当的时期内，乙醇（EtOH）暴露会导致发育中的海马区出现明显的神经毒性，并导致海马区神经发生持续性缺陷。右旋美托咪定（DEX）是一种高度选择性的α-2-肾上腺素能激动剂，已被证实可恢复神经损伤后齿状回（DG）中受损的神经发生和神经元可塑性。但是，DEX在EtOH诱导的海马体产后神经发生缺陷中的保护作用仍然未知。方法在暴露于EtOH之前对小鼠进行DEX预处理，以确定其对出生后海马神经发生受损的保护作用。对六日龄新生小鼠用DEX（125μg/ kg）或生理盐水处理，然后用Pt总量为5 g / kg的EtOH或等体积的生理盐水处理。免疫组织化学和免疫荧光用于评估DG中的神经发生和活化的小胶质细胞。实时荧光定量PCR（qRT-PCR）用于评估海马中炎症因子的表达。结果DEX预处理减弱了EtOH介导的海马神经发生的抑制和海马神经前体细胞（NPC）的减少。我们进一步证实，DEX预处理逆转了DG中EtOH诱导的小胶质细胞激活以及海马TNFα，MCP-1，IL-6和IL-1βmRNA水平的上调。结论我们的发现表明，DEX预处理可防止EtOH介导的对出生后小鼠海马神经发生的抑制，并通过抑制小胶质细胞的活化和炎性细胞因子的表达来逆转EtOH诱导的神经炎症。