Growth hormone secretagogue receptor signaling in the supramammillary nucleus targets nitric oxide-producing neurons and controls recognition memory in mice
Growth hormone secretagogue receptor signaling in the supramammillary nucleus targets nitric oxide-producing neurons and controls recognition memory in mice
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DOI：
10.1016/j.psyneuen.2022.105716
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发表时间：
2022-03-12
影响因子：
3.7
通讯作者：
Perello, Mario
中科院分区：
文献类型：
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作者：
Aguggia, Julieta P.;Cornejo, Maria P.;Perello, Mario
胃促生长素是一种胃源性激素，通过生长激素促分泌受体（GHSR）起作用。最近的证据表明，胃饥饿素的一些作用可能是通过乳上核（SuM）介导的。胃饥饿素不仅能与小鼠SuM内的细胞结合，还能激活SuM细胞，并在SuM内注入胃饥饿素诱导大鼠进食。在目前的研究中，我们旨在进一步表征胃饥饿素在SuM中的作用。我们首先研究了在GHSR启动子下表达增强绿色荧光蛋白（eGFP）的小鼠模型（GHSR-eGFP小鼠）。我们发现GHSR-eGFP小鼠的SuM中含有大量的eGFP细胞，其中一些细胞表达神经元型一氧化氮合酶。中枢注射而非全身注射的ghrelin到达SuM，诱导c-Fos表达。此外，5天40%卡路里限制方案，而不是2天禁食方案，增加了GHSR-eGFP小鼠SuM中非egfp +细胞的c-Fos表达，而在GHSR-eGFP缺陷小鼠中，没有观察到卡路里限制诱导c-Fos的现象。暴露于暴饮暴食方案的饱足小鼠也增加了GHSR-eGFP小鼠SuM中非egfp +细胞中c-Fos的表达，以ghsr依赖的方式。最后，sum内注射的胃饥饿素对食物摄入、运动活动、行为唤醒或空间记忆没有明显影响，但增加了识别记忆。因此，我们提供了令人信服的GHSR SuM神经元的神经解剖学特征及其在小鼠中的行为意义。
Ghrelin is a stomach-derived hormone that acts via the growth hormone secretagogue receptor (GHSR). Recent evidence suggests that some of ghrelin's actions may be mediated via the supramammillary nucleus (SuM). Not only does ghrelin bind to cells within the mouse SuM, but ghrelin also activates SuM cells and intra-SuM ghrelin administration induces feeding in rats. In the current study, we aimed to further characterize ghrelin action in the SuM. We first investigated a mouse model expressing enhanced green fluorescent protein (eGFP) under the promoter of GHSR (GHSR-eGFP mice). We found that the SuM of GHSR-eGFP mice contains a significant amount of eGFP cells, some of which express neuronal nitric oxide synthase. Centrally-, but not systemically-, injected ghrelin reached the SuM, where it induced c-Fos expression. Furthermore, a 5-day 40% calorie restriction protocol, but not a 2-day fast, increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice, whereas c-Fos induction by calorie restriction was not observed in GHSR-deficient mice. Exposure of satiated mice to a binge-like eating protocol also increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice in a GHSR-dependent manner. Finally, intra-SuM-injected ghrelin did not acutely affect food intake, locomotor activity, behavioral arousal or spatial memory but increased recognition memory. Thus, we provide a compelling neuroanatomical characterization of GHSR SuM neurons and its behavioral implications in mice.