Photoperiodic changes in hippocampal neurogenesis and plasma metabolomic profiles in relation to depression-like behavior in mice
Photoperiodic changes in hippocampal neurogenesis and plasma metabolomic profiles in relation to depression-like behavior in mice
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DOI：
10.1016/j.bbr.2021.113136
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发表时间：
2021-01
影响因子：
2.7
通讯作者：
Emi Taniguchi;Ayako Tashiro;Ayumi Hattori;M. Furuse;S. Yasuo
中科院分区：
文献类型：
--
作者：
Emi Taniguchi;Ayako Tashiro;Ayumi Hattori;M. Furuse;S. Yasuo
光周期改变了几种哺乳动物的情感行为和脑神经可塑性。我们研究了神经可塑性的关键调节因子胰岛素样生长因子-I(IGF-I)在C57BL/6J小鼠中的神经发生和信号通路是否受光周期的调节，C57BL/6J小鼠是季节性情感障碍的假定模型。我们还研究了光周期对与抑郁样行为相关的血浆代谢谱的影响，以了解外周代谢和行为之间可能的联系。与短日照(SD)组相比，长日照(LD)组小鼠海马齿状回5-溴-2‘-脱氧尿嘧啶核苷阳性细胞数和星形胶质细胞标记物水平较高。LD组小鼠血浆IGF-I水平和参与神经元增殖和分化的海马区IGF-I信号分子(BRN-4、NeuroD1和磷酸化Akt)水平/表达水平均高于LD组。使用LD和SD状态下的小鼠血浆进行的代谢组分析发现，几种代谢物与强迫游泳测试中的不动高度相关，强迫游泳测试是一种类似抑郁的行为。23种代谢物的水平与行为呈负相关，包括与运动的神经发生和抗抑郁药样作用有关的代谢物，精氨酸生物合成的代谢物，以及支链氨基酸的出现。有三种代谢物与这种行为呈正相关，其中包括一种神经毒素--胍基琥珀酸。综上所述，海马区神经发生和神经胶质组织的光周期反应可能通过包括IGF-I和外周代谢物在内的多个途径参与抑郁症行为的光周期改变。
Photoperiod alters affective behaviors and brain neuroplasticity in several mammalian species. We addressed whether neurogenesis and signaling pathways of insulin-like growth factor-I (IGF-I), a key modulator of neuroplasticity, are regulated by photoperiod in C57BL/6 J mice, a putative model of seasonal affective disorder. We also examined the effects of photoperiod on plasma metabolomic profiles in relation to depression-like behavior to understand a possible linkage between peripheral metabolism and behavior. Mice that were maintained under long-day conditions (LD) exhibited a higher number of 5-bromo-2′-deoxyuridine-positive cells and higher levels of astrocyte marker in the dentate gyrus of the hippocampus compared to that of mice under short-day conditions (SD). Plasma IGF-I levels and levels/expression of IGF-I signaling molecules in the hippocampus (Brn-4, NeuroD1, and phospho-Akt) involved in neuronal proliferation and differentiation were higher in the mice under LD. Metabolome analysis using plasma of the mice under LD and SD identified several metabolites that were highly correlated with immobility in the forced swim test, a depression-like behavior. Negative correlations with behavior occurred in the levels of 23 metabolites, including metabolites related to neurogenesis and antidepressant-like effects of exercise, metabolites in the biosynthesis of arginine, and the occurrence of branched chain amino acids. Three metabolites had positive correlations with the behavior, including guanidinosuccinic acid, a neurotoxin. Taken together, photoperiodic responses of neurogenesis and neuro-glial organization in the hippocampus may be involved in photoperiodic alteration of depression-like behavior, mediated through multiple pathways, including IGF-I and peripheral metabolites.