Department of Neurology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province.
Department of Neurology, Guangdong Sanjiu Brain Hospital, Guangzhou, Guangdong Province, People's Republic of China.
Neuroreport. 2021 Mar 3;32(4):321-325. doi: 10.1097/WNR.0000000000001591.
Studies have found that fibroblast growth factor 9 (FGF9) might have a negative effect in the psychiatric diseases, such as depression or anxiety, but its potential role in the pathophysiology of poststroke depression (PSD) remains uncertain. Here, we set out to investigate the expression changes of FGF9 and its receptors in PSD rats. Middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress was used to establish the PSD rat model. Then, the rats were randomly divided into four groups: control (sham-operation), MCAO, PSD and treated (fluoxetine injection by intraperitoneal). Weight measurement, sucrose preference test, open-field test and forced swim test were performed to evaluate the behavioral changes, and then Western blot and real-time quantitative PCR were used to detect the expression level of FGF9, fibroblast growth factor receptor 1 (FGFR1) and receptor 3 (FGFR3) in the dentate gyrus of rat hippocampus. We found that FGF9 protein and mRNA expression increased significantly in the MCAO and PSD groups; FGFR3 protein and mRNA expression decreased significantly in the MCAO and PSD groups; FGFR1 protein and mRNA expression decreased significantly in the PSD group, but increased in the treated group. Furthermore, the changes mentioned above were reversed obviously by fluoxetine. These results indicated that upregulated FGF9 expression and downregulated FGFR1 and FGFR3 expression may be involved in the pathogenesis of PSD, and the FGF9/FGFR signaling pathway may be considered as an attractive target for further study.
研究发现成纤维细胞生长因子 9(FGF9)可能在精神疾病中(如抑郁症或焦虑症)具有负面作用,但它在卒中后抑郁(PSD)病理生理学中的潜在作用仍不确定。在这里,我们着手研究 FGF9 及其受体在 PSD 大鼠中的表达变化。采用大脑中动脉闭塞(MCAO)联合慢性不可预测性轻度应激来建立 PSD 大鼠模型。然后,将大鼠随机分为四组:对照组(假手术)、MCAO 组、PSD 组和治疗组(腹腔注射氟西汀)。体重测量、蔗糖偏好试验、旷场试验和强迫游泳试验用于评估行为变化,然后使用 Western blot 和实时定量 PCR 检测大鼠海马齿状回中 FGF9、成纤维细胞生长因子受体 1(FGFR1)和受体 3(FGFR3)的表达水平。我们发现 FGF9 蛋白和 mRNA 表达在 MCAO 和 PSD 组中显著增加;FGFR3 蛋白和 mRNA 表达在 MCAO 和 PSD 组中显著降低;FGFR1 蛋白和 mRNA 表达在 PSD 组中显著降低,但在治疗组中增加。此外,氟西汀明显逆转了上述变化。这些结果表明,上调的 FGF9 表达和下调的 FGFR1 和 FGFR3 表达可能参与 PSD 的发病机制,FGF9/FGFR 信号通路可能被认为是进一步研究的有吸引力的靶点。