抑郁症经常发生在创伤性脑损伤(TBI)之后。然而,纤调蛋白(FMOD)在TBI相关性抑郁症中的作用尚不清楚。先前的研究表明FMOD是TBI的潜在关键因素,但其与TBI后抑郁的关联及其潜在机制尚不清楚.使用qPCR测量创伤性脑损伤患者的血清FMOD水平。使用自我抑郁量表(SDS)评估抑郁症的严重程度。神经功能,抑郁状态,使用改良的神经严重程度评分(mNSS)评估小鼠的认知功能,强迫游泳试验(FST)尾部悬挂试验(TST),蔗糖优选试验(SPT),和莫里斯水迷宫(MWM)。通过免疫荧光法揭示小鼠海马突触和神经元树突棘的形态学特征,透射电子显微镜,和高尔基考克斯染色。FMOD的蛋白表达水平,MAP2,SYP,和PSD95,以及PI3K/AKT/mTOR信号通路的磷酸化水平,通过蛋白质印迹检测到。TBI患者血清中FMOD水平降低。FMOD的过表达保留了神经元功能并减轻了抑郁样行为,突触蛋白表达增加,并诱导海马神经元超微结构改变。PI3K的磷酸化增加,AKT,mTOR提示PI3K/AKT/mTOR信号通路参与FMOD的保护作用。FMOD具有作为与TBI相关的抑郁症的治疗靶标的潜力,其保护作用可能通过PI3K/AKT/mTOR信号通路介导。
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.