Ethanol consumption activates a subset of arcuate nucleus pro-opiomelanocortin (POMC)-producing neurons: a c-fos immunohistochemistry study.
Ethanol consumption activates a subset of arcuate nucleus pro-opiomelanocortin (POMC)-producing neurons: a c-fos immunohistochemistry study.
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DOI：
10.14814/phy2.15231
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发表时间：
2022-03
影响因子：
2.5
通讯作者：
Olive MF
中科院分区：
文献类型：
--
作者：
Hood LE;Nagy EK;Leyrer-Jackson JM;Olive MF
乙醇会激活大脑内各种含有阿片肽的回路，这可能是其激励和奖励作用的基础。该回路的一个组成部分由位于下丘脑弓状核 (ArcN) 的神经元组成，这些神经元表达阿片黑皮质素原 (POMC)，这是一种阿片类药物前体肽，可被裂解形成生物活性片段，包括 β-内啡肽和 α-黑素细胞刺激激素。在这项研究中，我们试图通过立即早期基因 c-fos 的表达来确定乙醇摄入是否会激活 ArcN POMC 神经元。雄性和雌性 POMC-EGFP 小鼠连续 3 天（2 小时/天）接受黑暗饮酒 (DID) 程序，并允许饮用乙醇 (20% v/v)、糖精 (0.2% w/v) 或水。在 DID 程序的第四天，允许动物消耗各自的溶液 20 分钟，并在会话后 1 小时收获大脑并进行处理，进行 c-fos 免疫组织化学分析以及与 EGFP 的共定位。我们的结果表明，乙醇摄入会激活 ArcN POMC 神经元的子集 (~15–20%)，而糖精或水摄入会激活这些神经元的数量明显较少 (~5–12%)。激活的 POMC 神经元的百分比与组织采集时的血液乙醇水平不相关，并且激活似乎分布在整个 ArcN 的头尾轴上。饮用溶液的神经元激活程度没有观察到性别差异。这些发现表明，乙醇消耗会优先激活 ArcN POMC 神经元，这强化了乙醇激活大脑中内源性阿片类系统的观点，这可能是其动机特性的基础。乙醇消耗会激活 ArcN 内的 POMC 神经元子集，这些神经元似乎遍布大部分头尾轴。糖精和水的消耗对 POMC 神经元的激活程度较小。
Ethanol activates various opioid peptide‐containing circuits within the brain that may underlie its motivational and rewarding effects. One component of this circuitry consists of neurons located in the arcuate nucleus (ArcN) of the hypothalamus which express pro‐opiomelanocortin (POMC), an opioid precursor peptide that is cleaved to form bioactive fragments including β‐endorphin and α‐melanocyte stimulating hormone. In this study, we sought to determine if ethanol intake activates ArcN POMC neurons as measured by expression of the immediate early gene c‐fos. Male and female POMC‐EGFP mice underwent drinking‐in‐the‐dark (DID) procedures for 3 consecutive days (2 h/day) and were allowed to consume either ethanol (20% v/v), saccharin (0.2% w/v), or water. On the fourth day of DID procedures, animals were allowed to consume their respective solutions for 20 min, and 1 h following the session brains were harvested and processed for c‐fos immunohistochemistry and co‐localization with EGFP. Our results indicate that ethanol intake activates a subset (~15–20%) of ArcN POMC neurons, whereas saccharin or water intake activates significantly fewer (~5–12%) of these neurons. The percent of activated POMC neurons did not correlate with blood ethanol levels at the time of tissue collection, and activation appeared to be distributed throughout the rostrocaudal axis of the ArcN. No sex differences were observed in the degree of neuronal activation across drinking solutions. These findings indicate a preferential activation of ArcN POMC neurons by ethanol consumption, strengthening the notion that ethanol activates endogenous opioid systems in the brain which may underlie its motivational properties. Ethanol consumption activates a subset of POMC neurons within the ArcN, which appear to be throughout most of the rostrocaudal axis. Saccharin and water consumption has lesser degrees of POMC neuronal activation.