Taniguchi Emi, Tashiro Ayako, Hattori Ayumi, Furuse Mitsuhiro, Yasuo Shinobu
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Behav Brain Res. 2021 Apr 9;403:113136. doi: 10.1016/j.bbr.2021.113136. Epub 2021 Jan 20.
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.
光照周期会改变几种哺乳动物的情感行为和大脑神经可塑性。我们研究了神经发生以及胰岛素样生长因子-I（IGF-I，神经可塑性的关键调节因子）的信号通路是否受光照周期调节，C57BL/6 J小鼠是季节性情感障碍的假定模型。我们还研究了光照周期对与抑郁样行为相关的血浆代谢组学谱的影响，以了解外周代谢与行为之间可能的联系。与短日照条件（SD）下的小鼠相比，长期处于长日照条件（LD）下的小鼠在海马齿状回中表现出更多的5-溴-2'-脱氧尿苷阳性细胞和更高水平的星形胶质细胞标志物。长期处于长日照条件下的小鼠血浆IGF-I水平以及海马中参与神经元增殖和分化的IGF-I信号分子（Brn-4、NeuroD1和磷酸化Akt）的水平/表达更高。使用长期处于长日照和短日照条件下的小鼠血浆进行代谢组分析，确定了几种与强迫游泳试验中的不动行为（一种抑郁样行为）高度相关的代谢物。23种代谢物的水平与行为呈负相关，包括与神经发生和运动的抗抑郁样作用相关的代谢物、精氨酸生物合成中的代谢物以及支链氨基酸的出现。三种代谢物与行为呈正相关，包括神经毒素胍基琥珀酸。综上所述，海马中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种途径参与抑郁样行为的光周期改变。
