Early weaning increases anxiety via brain-derived neurotrophic factor signaling in the mouse prefrontal cortex
Early weaning increases anxiety via brain-derived neurotrophic factor signaling in the mouse prefrontal cortex
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早期断奶通过小鼠前额皮质中的脑源性神经营养因子信号传导增加焦虑
DOI：
10.1038/s41598-019-40530-9
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发表时间：
2019
影响因子：
4.6
通讯作者：
Mogi Kazutaka
中科院分区：
文献类型：
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作者：
Kikusui Takefumi;Kanbara Natsumi;Ozaki Mariya;Hirayama Nozomi;Ida Kumiko;Tokita Mika;Tanabe Naho;Mitsuyama Kuriko;Abe Hatsuki;Yoshida Miki;Nagasawa Miho;Mogi Kazutaka
早期发育中母体护理的剥夺明显影响情绪发育，但其潜在的神经分子机制尚不完全清楚。在母婴关系中断的小鼠模型中，早期断奶会对幼崽产生长期影响，使它们在成年后表现出皮质酮分泌增加、焦虑和应激反应。揭示其背后的分子机制，将有利于缓解儿童期虐待所引发的心理问题。我们报告，无论是在成年期还是在断奶后不久，在早期断奶的小鼠中使循环皮质酮正常化，可以改善在加迷宫测试中评估的焦虑水平。将糖皮质激素受体拮抗剂注射到前额叶皮质(PFC)可以逆转早期断奶的效果，而注射皮质酮则会增加焦虑水平，这表明PFC是皮质酮的目标大脑区域。在早期断奶小鼠的PFC中，我们观察到脑源性神经营养因子(BDNF)和相关mRNAs的表达长期减少。早期断奶小鼠的焦虑可通过预先给予BDNF或BDNF受体激动剂来改善。综上所述，早期断奶通过调节PFC中的糖皮质激素和BDNF信号来增加焦虑水平。
Deprivation of maternal care during early development markedly affects emotional development, but the underlying neuromolecular mechanisms are not fully understood. In a mouse model of disrupted mother-infant relationship, early weaning causes long-term impacts on pups to exhibit increased corticosterone secretion, anxiety, and stress responses in their adulthood. Revealing the molecular mechanisms behind it would beneficial to ameliorating mental problems caused by abuse in childhood. We report that normalizing circulating corticosterone in early-weaned mice, either in adulthood or soon after weaning, ameliorated anxiety levels assessed in the plus maze test. Administering a glucocorticoid receptor antagonist into the prefrontal cortex (PFC) reversed the effects of early weaning, whereas administering corticosterone increased anxiety levels, suggesting that the PFC is corticosterone’s target brain region. In the PFCs of early-weaned mice, we observed prolonged reductions in the expression of brain-derived neurotrophic factor (BDNF) and associated mRNAs. Anxiety in early-weaned mice was ameliorated by pretreatment with BDNF or a BDNF receptor agonist. In summary, early weaning increased anxiety levels by modulating glucocorticoid and BDNF signaling in the PFC.