Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours
Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours
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代谢型谷氨酸受体亚型 7 在内分泌系统和社会行为的调节中具有关键作用
DOI：
10.1111/jne.12575
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发表时间：
2018
影响因子：
3.2
通讯作者：
Kawauchi A.
中科院分区：
文献类型：
--
作者：
Masugi-Tokita M;Yoshida T;Kageyama S;Kawata M;Kawauchi A.
代谢型谷氨酸受体亚型7(MGluR7)是第三类mGluR的一种，通过Gi/Go蛋白与腺苷环化酶负偶联，定位于哺乳动物中枢神经系统的突触前活动区。我们之前曾报道，mGluR7对于男性间攻击和杏仁核依赖恐惧学习是必不可少的。为了阐明mGluR7在神经内分泌系统中的作用，我们进行了生化分析，发现mGluR7基因敲除(KO)小鼠的睾酮水平显著降低。睾丸激素替代使去势野生型小鼠的雄性间攻击行为恢复到性腺完整的野生型小鼠的水平。然而，在给予相同剂量的睾丸激素替代的情况下，mGluR7 KO小鼠几乎没有表现出攻击性行为。这些结果表明，血浆睾酮水平的降低与mGluR7KO小鼠雄性间攻击行为的缺陷无关。完整的mGluR7 KO小鼠的社会调查行为也不同于野生型小鼠；例如，KO小鼠表现出较少的肛门嗅探和更频繁的梳理行为。睾酮替代增加了去势的mGluR7 KO小鼠的肛门嗅闻和梳理行为，而去势的野生型小鼠和接受睾酮替代的KO小鼠之间的差异仍然存在。这些结果表明，血浆睾酮水平的降低可能部分抑制了完整mGluR7KO小鼠的社会调查行为。此外，去势的mGluR7 KO小鼠的精囊比去势的野生型小鼠小，尽管完整小鼠的精囊重量正常。这些观察表明，在mGluR7 KO小鼠中，除了睾丸睾酮外，其他一些激素水平可能是失调的，表明mGluR7在内分泌系统中起着关键作用。综上所述，我们的发现表明，除了男性之间的攻击和恐惧反应等先天行为外，mGluR7对内分泌系统的调节也是必不可少的。
Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localised to presynaptic active zones of the mammalian central nervous system. We previously reported that mGluR7 is essential for intermale aggression and amygdala‐dependent fear learning. To elucidate the role of mGluR7 in the neuroendocrine system, we performed biochemical analyses and found a significant reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone replacement restored intermale aggressive behaviour in castrated wild‐type mice to the level of gonadally intact wild‐type mice. However, given the same dosage of testosterone replacement, mGluR7 KO mice showed almost no aggressive behaviour. These results indicate that reduction of plasma testosterone is unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social investigating behaviour of intact mGluR7 KO mice also differed from that of wild‐type mice; e.g. the KO mice showing less frequent anogenital sniffing and more frequent grooming behaviour. Testosterone replacement increased anogenital sniffing and grooming behaviour in castrated mGluR7 KO mice, while the differences were still present between castrated wild‐type mice and KO mice after both underwent testosterone replacement. These results imply that reduction of plasma testosterone may partially inhibit social investigating behaviours in intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal vesicles than those of castrated wild‐type mice, although seminal vesicle weights were normal in intact mice. These observations suggest that, besides testicular testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice, and indicate a critical role of mGluR7 in the endocrine system. Taken together, our findings demonstrate that mGluR7 is essential for the regulation of the endocrine system, in addition to innate behaviours such as intermale aggression and fear response.