Roles of fibroblast growth factor 21 in the control of depression-like behaviours after social defeat stress in male rodents,Journal of Neuroendocrinology

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Roles of fibroblast growth factor 21 in the control of depression-like behaviours after social defeat stress in male rodents
Journal of Neuroendocrinology ( IF 3.3 ) Pub Date : 2021-08-09 , DOI: 10.1111/jne.13026
Naoki Usui _{1,

2} , Masahide Yoshida ₁ , Yuki Takayanagi ₁ , Naranbat Nasanbuyan ₁ , Ayumu Inutsuka ₁ , Hiroshi Kurosu ₃ , Hiroaki Mizukami ₄ , Yoshiyuki Mori ₂ , Makoto Kuro-O ₃ , Tatsushi Onaka ₁

Affiliation

Fibroblast growth factor 21 (FGF21) modulates energy metabolism and neuroendocrine stress responses. FGF21 synthesis is increased after environmental or metabolic challenges. Detailed roles of FGF21 in the control of behavioural disturbances under stressful conditions remain to be clarified. Here, we examined the roles of FGF21 in the control of behavioural changes after social defeat stress in male rodents. Central administration of FGF21 increased the number of tyrosine hydroxylase-positive catecholaminergic cells expressing c-Fos protein, an activity marker of neurones, in the nucleus tractus solitarius and area postrema. Double in situ hybridisation showed that some catecholaminergic neurones in the dorsal medulla oblongata expressed β-Klotho, an essential co-receptor for FGF21, in male mice. Social defeat stress increased FGF21 concentrations in the plasma of male mice. FGF21-deficient male mice showed social avoidance in a social avoidance test with C57BL/6J mice (background strain of FGF21-deficient mice) and augmented immobility behaviour in a forced swimming test after social defeat stress. On the other hand, overexpression of FGF21 by adeno-associated virus vectors did not significantly change behaviours either in wild-type male mice or FGF21-deficient male mice. The present data are consistent with the view that endogenous FGF21, possibly during the developmental period, has an inhibitory action on stress-induced depression-like behaviour in male rodents.

中文翻译：

成纤维细胞生长因子 21 在控制雄性啮齿动物社交失败应激后抑郁样行为中的作用

成纤维细胞生长因子 21 (FGF21) 调节能量代谢和神经内分泌应激反应。在环境或代谢挑战后，FGF21 合成会增加。 FGF21 在压力条件下控制行为障碍中的详细作用仍有待阐明。在这里，我们研究了 FGF21 在控制雄性啮齿动物社交失败压力后行为变化中的作用。 FGF21的中枢给药增加了孤束核和后区中表达c-Fos蛋白（神经元活动标记物）的酪氨酸羟化酶阳性儿茶酚胺能细胞的数量。双原位杂交表明，雄性小鼠延髓背侧的一些儿茶酚胺能神经元表达 β-Klotho，这是 FGF21 的重要辅助受体。社交失败压力增加了雄性小鼠血浆中 FGF21 的浓度。 FGF21 缺陷型雄性小鼠在 C57BL/6J 小鼠（FGF21 缺陷型小鼠的背景品系）的社交回避测试中表现出社交回避，并在社交失败压力后的强迫游泳测试中表现出增强的不动行为。另一方面，腺相关病毒载体过度表达 FGF21 并没有显着改变野生型雄性小鼠或 FGF21 缺陷型雄性小鼠的行为。目前的数据与以下观点一致：内源性 FGF21 可能在发育期间对雄性啮齿类动物应激诱发的抑郁样行为具有抑制作用。

更新日期：2021-10-15

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