FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Xuekang Huang, Ziyu Zhu, Mengran Du, Chenrui Wu, Jiayuanyuan Fu, Jie Zhang, Weilin Tan, Biying Wu, Lian Liu, Z B Liao
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Abstract

Depression frequently occurs following traumatic brain injury (TBI). However, the role of Fibromodulin (FMOD) in TBI-related depression is not yet clear. Previous studies have suggested FMOD as a potential key factor in TBI, yet its association with depression post-TBI and underlying mechanisms are not well understood. Serum levels of FMOD were measured in patients with traumatic brain injury using qPCR. The severity of depression was assessed using the self-depression scale (SDS). Neurological function, depressive state, and cognitive function in mice were assessed using the modified Neurological Severity Score (mNSS), forced swimming test (FST), tail suspension test (TST), Sucrose Preference Test (SPT), and morris water maze (MWM). The morphological features of mouse hippocampal synapses and neuronal dendritic spines were revealed through immunofluorescence, transmission electron microscopy, and Golgi-Cox staining. The protein expression levels of FMOD, MAP2, SYP, and PSD95, as well as the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway, were detected through Western blotting. FMOD levels were decreased in TBI patients' serum. Overexpression of FMOD preserved neuronal function and alleviated depression-like behaviour, increased synaptic protein expression, and induced ultrastructural changes in hippocampal neurons. The increased phosphorylation of PI3K, AKT, and mTOR suggested the involvement of the PI3K/AKT/mTOR signaling pathway in FMOD's protective effects. FMOD exhibits potential as a therapeutic target for depression related to TBI, with its protective effects potentially mediated through the PI3K/AKT/mTOR signaling pathway.

Abstract Image

FMOD通过靶向创伤性脑损伤后的PI3K/AKT/mTOR信号传导缓解抑郁行为
创伤性脑损伤(TBI)后经常会出现抑郁症。然而,纤维调节蛋白(FMOD)在创伤性脑损伤相关抑郁症中的作用尚不明确。以前的研究表明,FMOD 是创伤性脑损伤的潜在关键因素,但其与创伤性脑损伤后抑郁的关系及其内在机制尚不十分清楚。本研究采用 qPCR 方法测量了创伤性脑损伤患者血清中的 FMOD 水平。抑郁的严重程度采用自我抑郁量表(SDS)进行评估。使用改良神经严重程度评分(mNSS)、强迫游泳试验(FST)、尾悬试验(TST)、蔗糖偏好试验(SPT)和莫里斯水迷宫(MWM)评估小鼠的神经功能、抑郁状态和认知功能。通过免疫荧光、透射电子显微镜和高尔基-考克斯染色法观察了小鼠海马突触和神经元树突棘的形态特征。通过 Western 印迹检测了 FMOD、MAP2、SYP 和 PSD95 的蛋白表达水平以及 PI3K/AKT/mTOR 信号通路的磷酸化水平。在创伤性脑损伤患者的血清中,FMOD的水平有所下降。过表达 FMOD 可保护神经元功能,缓解抑郁样行为,增加突触蛋白表达,诱导海马神经元超微结构变化。PI3K、AKT和mTOR磷酸化的增加表明,PI3K/AKT/mTOR信号通路参与了FMOD的保护作用。FMOD 有可能成为创伤性脑损伤相关抑郁症的治疗靶点,其保护作用可能是通过 PI3K/AKT/mTOR 信号通路介导的。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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