Martin Hugo, Bullich Sébastien, Guiard Bruno P, Fioramonti Xavier
NutriNeuro, UMR 1286 INRAE, Bordeaux INP, Bordeaux University, Bordeaux, France.
Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), CNRS UMR5169, UPS, Université de Toulouse, Toulouse, France.
J Neuroendocrinol. 2021 Jan 28;33(4):e12928. doi: 10.1111/jne.12928.
The idea that insulin could influence emotional behaviours has long been suggested. However, the underlying mechanisms have yet to be solved and there is no direct and clear-cut evidence demonstrating that such action involves brain serotonergic neurones. Indeed, initial arguments in favour of the association between insulin, serotonin and mood arise from clinical or animal studies showing that impaired insulin action in type 1 or type 2 diabetes causes anxiety- and depressive symptoms along with blunted plasma and brain serotonin levels. The present review synthesises the main mechanistic hypotheses that might explain the comorbidity between diabetes and depression. It also provides a state of knowledge of the direct and indirect experimental evidence that insulin modulates brain serotonergic neurones. Finally, it highlights the literature suggesting that antidiabetic drugs present antidepressant-like effects and, conversely, that serotonergic antidepressants impact glucose homeostasis. Overall, this review provides mechanistic insights into how insulin signalling alters serotonergic neurotransmission and related behaviours bringing new targets for therapeutic options.
长期以来，人们一直认为胰岛素可能会影响情绪行为。然而，其潜在机制尚未得到解决，也没有直接明确的证据表明这种作用涉及脑血清素能神经元。事实上，最初支持胰岛素、血清素与情绪之间关联的观点来自临床或动物研究，这些研究表明1型或2型糖尿病患者胰岛素作用受损会导致焦虑和抑郁症状，同时血浆和脑血清素水平降低。本综述综合了可能解释糖尿病与抑郁症共病的主要机制假说。它还提供了关于胰岛素调节脑血清素能神经元的直接和间接实验证据的知识现状。最后，它强调了文献表明抗糖尿病药物具有类抗抑郁作用，反之，血清素能抗抑郁药会影响葡萄糖稳态。总体而言，本综述提供了关于胰岛素信号如何改变血清素能神经传递及相关行为的机制见解，为治疗选择带来了新靶点。
