Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats.
Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats.
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DOI：
10.1038/s41398-022-02210-7
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发表时间：
2022-10-10
影响因子：
6.8
通讯作者：
Haj-Dahmane, Samir
中科院分区：
文献类型：
--
作者：
Oubraim, Saida;Wang, Ruixiang;Hausknecht, Kathryn;Kaczocha, Martin;Shen, Roh-Yu;Haj-Dahmane, Samir
产前酒精暴露（PE）引起的情绪障碍（包括焦虑和抑郁）是胎儿酒精谱系障碍（FASD）的常见症状。产前乙醇暴露与几种神经递质系统的持续功能障碍有关，包括在情绪调节和应激稳态中起主要作用的5-羟色胺（5-HT）系统。虽然已知PE会破坏5-HT系统的发育，但其改变中缝背核（DRn）5-HT神经元功能及其突触输入的细胞机制仍不清楚。在这里，我们在妊娠第8 - 20天使用了孕中期狂饮模式PE（每天两次以3 g/kg的剂量灌胃15% w/v乙醇，间隔5-6 h），并使用升高的正（zero）和零（ZM）迷宫测量了成年雄性大鼠的焦虑样行为。我们还采用离体电生理和药理学方法来阐明PE改变DRn 5-HT神经元兴奋性和突触传递的机制。我们发现PE增强了成年雄性大鼠的焦虑样行为，并诱导了DRn 5-HT神经元的持续激活。PE诱导的DRn 5-HT神经元的激活在很大程度上是通过增强DRn谷氨酸突触介导的，这是由氮能系统的激活和内源性大麻素信号转导受损引起的。因此，本研究揭示了“推拉”效应的PE对氮能和eCB信号，分别介导的DRn 5-HT神经元的活性增强，并可能有助于在FASD动物模型中观察到的焦虑样行为。
Mood disorders, including anxiety and depression caused by prenatal ethanol exposure (PE) are prevalent conditions in fetal alcohol spectrum disorders (FASDs). Prenatal ethanol exposure is associated with persistent dysfunctions of several neurotransmitter systems, including the serotonin (5-HT) system, which plays a major role in mood regulation and stress homeostasis. While PE is known to disrupt the development of the 5-HT system, the cellular mechanisms by which it alters the function of dorsal raphe nucleus (DRn) 5-HT neurons and their synaptic inputs remain unknown. Here, we used a second-trimester binge-drinking pattern PE (two daily gavages of 15% w/v ethanol at 3 g/kg, 5–6 h apart) during gestational days 8 - 20 and measured anxiety-like behaviors of adult male rats using the elevated plus (EPM) and zero (ZM) mazes. We also employed ex-vivo electrophysiological and pharmacological approaches to unravel the mechanisms by which PE alters the excitability and synaptic transmission onto DRn 5-HT neurons. We found that PE enhanced anxiety-like behaviors in adult male rats and induced a persistent activation of DRn 5-HT neurons. The PE-induced activation of DRn 5-HT neurons was largely mediated by potentiation of DRn glutamate synapses, which was caused by activation of the nitrergic system and impaired endocannabinoid signaling. As such, the present study reveals “push-pull” effects of PE on nitrergic and eCB signaling, respectively, which mediate the enhanced activity of DRn 5-HT neurons and could contribute to anxiety-like behaviors observed in animal model of FASD.
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影响因子：
3.4
作者：
Dolzani SD;Baratta MV;Amat J;Agster KL;Saddoris MP;Watkins LR;Maier SF
通讯作者：
Maier SF
影响因子：
--
作者：
Alati, Rosa;Al Mamun, Abdullah;Bor, William
通讯作者：
Bor, William
影响因子：
4.7
作者：
Brocardo, Patricia S.;Boehme, Fanny;Christie, Brian R.
通讯作者：
Christie, Brian R.
影响因子：
1.7
作者：
Boseck, Justin J.;Davis, Andrew S.;Gelder, Barbara C.
通讯作者：
Gelder, Barbara C.
影响因子：
--
作者：
Bradley SA;Steinert JR
通讯作者：
Steinert JR