Ciliary neurotrophic factor is a key sex-specific regulator of depressive-like behavior in mice.
Ciliary neurotrophic factor is a key sex-specific regulator of depressive-like behavior in mice.
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DOI：
10.1016/j.psyneuen.2018.09.038
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发表时间：
2019-03
影响因子：
3.7
通讯作者：
Hagg T
中科院分区：
文献类型：
--
作者：
Jia C;Brown RW;Malone HM;Burgess KC;Gill WD;Keasey MP;Hagg T
睫状神经营养因子（CNTF）由星形胶质细胞产生，可促进神经发生和神经保护。关于CNTF在情感行为中的作用知之甚少。我们通过强迫游泳、蔗糖偏好和高架T型迷宫测试，研究了CNTF是否影响成年小鼠的抑郁样和焦虑样行为。在强迫游泳测试中，雌性野生型CNTF +/+小鼠比雄性CNTF +/+同窝小鼠更容易出现行为绝望，表现为不动时间增加和不动潜伏期缩短。CNTF -/-小鼠缺乏CNTF对雌性小鼠（不动时间减少和蔗糖偏好增加）和雄性小鼠（不动时间增加）的抑郁样行为有相反的影响。雌性野生型小鼠在杏仁核中表达的CNTF比雄性小鼠多。卵巢切除增加了CNTF的表达以及不动时间，而在CNTF -/-小鼠中不动时间显著减少，这表明CNTF介导了卵巢切除诱导的不动时间，可能是在杏仁核中。孕酮而非17 -β雌二醇抑制培养的C6星形胶质瘤细胞中CNTF的表达。孕酮处理也降低了雌性CNTF +/+小鼠杏仁核中CNTF的表达并减少了不动时间，但在CNTF -/-小鼠中没有这种作用。去势不改变雄性小鼠的CNTF表达及其行为。最后，CNTF对高架T型迷宫（一种焦虑行为测试）没有影响，这表明焦虑样行为可能有不同的机制。这项研究揭示了一种新的CNTF介导的应激诱导的抑郁样行为机制，并指出了针对抑郁症的性别特异性治疗的机会，例如女性使用孕酮，男性使用刺激CNTF的药物。
Ciliary neurotrophic factor (CNTF) is produced by astrocytes and promotes neurogenesis and neuroprotection. Little is known about the role of CNTF in affective behavior. We investigated whether CNTF affects depressive- and anxiety-like behavior in adult mice as tested in the forced swim, sucrose preference and elevated-T maze tests. Female wild type CNTF+/+ mice more readily developed behavioral despair with increased immobility time and decreased latency to immobility in the forced swim test than male CNTF+/+ littermates. The lack of CNTF in CNTF−/− mice had an opposite effect on depressive-like behavior in female mice (reduced immobility time and increased sucrose preference) vs. male mice (increased immobility time). Female wildtype mice expressed more CNTF in the amygdala than male mice. Ovariectomy increased CNTF expression, as well as immobility time, which was significantly reduced in CNTF−/− mice, suggesting that CNTF mediates overiectomy induced immobility time, possibly in the amygdala. Progesterone but not 17-β estradiol inhibited CNTF expression in cultured C6 astroglioma cells. Progesterone treatment also reduced CNTF expression in the amygdala and decreased immobility time in female CNTF+/+ but not in CNTF−/− mice. Castration did not alter CNTF expression in males nor their behavior. Lastly, there were no effects of CNTF on the elevated T-maze, a behavioral test of anxiety, suggesting that a different mechanism may underlie anxiety-like behavior. This study reveals a novel CNTF-mediated mechanism in stress-induced depressive-like behavior and points to opportunities for sex-specific treatments for depression, e.g. progesterone in females and CNTF-stimulating drugs in males.
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