FAM19A5/TAFA5, a novel neurokine, plays a crucial role in depressive-like and spatial memory-related behaviors in mice
FAM19A5/TAFA5, a novel neurokine, plays a crucial role in depressive-like and spatial memory-related behaviors in mice
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FAM19A5/TAFA5 是一种新型神经因子，在小鼠抑郁样和空间记忆相关行为中发挥着至关重要的作用
DOI：
10.1038/s41380-020-0720-x
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发表时间：
2020-04-21
影响因子：
11
通讯作者：
Wang, Ying
中科院分区：
文献类型：
--
作者：
Huang, Shiyang;Zheng, Can;Wang, Ying
FAM 19 A5/TAFA 5是具有序列相似性19的家族成员，在情绪和认知调节中具有未知功能。在此，我们报道了FAM 19 A5在胚胎和出生后小鼠脑中的高表达，尤其是在海马中。在行为上，Fam 19 a5基因缺失导致抑郁样行为增加，并损害了大脑皮层依赖的空间记忆。这些行为改变与α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体和N-甲基-D-天冬氨酸受体的表达减少以及海马中谷氨酸释放和神经元活性的显著减少有关。随后，这些变化导致树突棘密度降低。近年来，慢性应激在抑郁症发生发展中的作用日益明确，但其具体机制尚待阐明。我们发现慢性应激处理的小鼠血浆和海马中FAM 19 A5的水平显著降低，而在海马中选择性过表达人FAM 19 A5可以减轻慢性应激诱导的抑郁样行为。综上所述，我们的研究结果首次揭示了FAM 19 A5在海马的抑郁和空间认知调节中起着关键作用。本研究为慢性应激诱发抑郁症提供了新的机制，也为抑郁症的诊断提供了潜在的生物标志物，为抑郁症的治疗提供了新的策略。
FAM19A5/TAFA5 is a member of the family with sequence similarity 19 with unknown function in emotional and cognitive regulation. Here, we reported that FAM19A5 was highly expressed in the embryonic and postnatal mouse brain, especially in the hippocampus. Behaviorally, genetic deletion ofFam19a5resulted in increased depressive-like behaviors and impaired hippocampus-dependent spatial memory. These behavioral alterations were associated with the decreased expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and N-methyl-D-aspartic acid receptors, as well as significantly reduced glutamate release and neuronal activity in the hippocampus. Subsequently, these changes led to the decreased density of dendritic spines. In recent years, the roles of chronic stress participating in the development of depression have become increasingly clear, but the mechanism remains to be elucidated. We found that the levels of FAM19A5 in plasma and hippocampus of chronic stress-treated mice were significantly decreased whereas overexpression of human FAM19A5 selectively in the hippocampus could attenuate chronic stress-induced depressive-like behaviors. Taken together, our results revealed for the first time that FAM19A5 plays a key role in the regulation of depression and spatial cognition in the hippocampus. Furthermore, our study provided a new mechanism for chronic stress-induced depression, and also provided a potential biomarker for the diagnosis and a new strategy for the treatment of depression.