Abstract：
Depression is a neuropsychiatric disorder characterized by persistent pleasure loss and behavioral despair. However, the potential mechanisms and therapeutic targets for depression treatment remain unclear. Therefore, identifying the underlying pathogenesis of depression would promote the development of novel treatment and provide effective targets for antidepressant drugs. In this study, proteomics analysis showed that the expression level of phosphatase and actin regulator 4 (Phactr4) was significantly increased in the CA1 hippocampus of depressed rats. The upregulated Phactr4 might induce dysfunction of the synaptic structure via suppressing the p-LIMK/p-Cofilin signaling pathway, and promote neuroinflammation via activating the NF-κB/NLRP3 pathway, which ultimately contributes to the pathogenesis of depression. In contrast, the downregulation of Phactr4 in hippocampal CA1 of depressed rats alleviated depression-like behaviors, along with reducing neuroinflammation and improving synaptic plasticity. In conclusion, these findings provide evidence that Phactr4 plays an important role in regulating neuroinflammatory response and impairment of synaptic plasticity, effects seem to involve in the pathogenesis of depression, and Phactr4 may serve as a potential target for antidepressant treatment.
摘要：
抑郁症是一种神经精神疾病，其特征是持续的快感丧失和行为绝望。然而,抑郁症治疗的潜在机制和治疗靶点尚不清楚.因此,确定抑郁症的潜在发病机制将促进新型治疗方法的发展，并为抗抑郁药物提供有效的靶点。在这项研究中,蛋白质组学分析表明,抑郁大鼠海马CA1区磷酸酶和肌动蛋白调节因子4(Phactr4)的表达水平显著升高。上调的Phactr4可能通过抑制p-LIMK/p-Cofilin信号通路引起突触结构的功能障碍,并通过激活NF-κB/NLRP3通路促进神经炎症，最终导致抑郁症的发病机制。相比之下,抑郁大鼠海马CA1区Phactr4下调减轻抑郁样行为,同时减少神经炎症和改善突触可塑性。总之,这些发现提供了证据，表明Phactr4在调节神经炎症反应和突触可塑性损害中起重要作用，影响似乎涉及抑郁症的发病机制，和Phactr4可能作为抗抑郁治疗的潜在靶点。
