Neuroplastin 65 modulates anxiety- and depression-like behavior likely through adult hippocampal neurogenesis and central 5-HT activity
Neuroplastin 65 modulates anxiety- and depression-like behavior likely through adult hippocampal neurogenesis and central 5-HT activity
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Neuroplastin 65 可能通过成人海马神经发生和中枢 5-HT 活性调节焦虑和抑郁样行为
DOI：
10.1111/febs.14865
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发表时间：
2019-09-01
期刊：
影响因子：
5.4
通讯作者：
Yuan, Qionglan
中科院分区：
文献类型：
--
作者：
Li, Huanhuan;Liu, Yutong;Yuan, Qionglan
神经致活蛋白65（Np 65）是一种脑特异性细胞粘附分子，其在海马体、杏仁核和皮质中高度表达，这些区域是与记忆和情绪相关的脑区域。然而，Np 65在情绪行为调节中的作用仍不清楚。在本研究中，我们发现Np 65基因敲除（Np 65 KO）小鼠表现出焦虑样行为增强，抑郁样行为的某些方面减少，社交能力和记忆力增加。生物化学研究显示，Np 65 KO小鼠显示海马中成年出生的神经元和增殖增加。此外，海马5-羟色胺（5-HT）水平降低。脑干中色氨酸羟化酶2的表达和5-HT 3A受体的表达也降低。电生理记录证实Np 65 KO小鼠海马中长时程增强的维持受损。总之，我们的研究结果揭示了Np 65在调节焦虑和抑郁样行为中的作用，并表明Np 65可能对维持情绪稳定至关重要，这表明它可能是治疗精神疾病的一个有吸引力的潜在靶点。
Neuroplastin 65 (Np65) is a brain-specific cell adhesion molecule that is highly expressed in the hippocampus, amygdala, and cortex, regions of the brain that are associated with memory and emotions. However, the role of Np65 in regulation of emotional behavior is still unclear. In the present study, we show that Np65 knock-out (Np65 KO) mice display enhanced anxiety-like behavior, a reduction in some aspects of depressive-like behaviors, and increased sociability and memory. Biochemical investigations revealed that Np65 KO mice show increased adult-born neurons and proliferation in the hippocampus. In addition, the level of 5-hydroxytryptamine (5-HT) in the hippocampus was reduced. The expression of tryptophan hydroxylase 2 in the brainstem and the expression of the 5-HT3A receptor were also decreased. Electrophysiological recordings confirmed an impaired maintenance of long-term potentiation in the hippocampus of Np65 KO mice. Together, our findings uncover a role for Np65 in regulating anxiety- and depressive-like behaviors and suggest that Np65 may be essential for the maintenance of emotional stability, indicating that it might be an attractive potential target for treatment of psychiatric disorders.