Bi Bin-Yu, Lin Lin, Huang Liu, Zhou Jun, Yan Wei-Juan, Huang Ling, Wang Jie, Li Xue-Bin
Youjiang Medical University for Nationalities, No. 98 Chengxiang Road, Youjiang District,, Guangxi Zhuang Autonomous Region,, 533000,, Baise, China.
Youjiang Medical University for Nationalities Affiliated Hospital, No. 18 Zhongshan 2nd Road, Youjiang District, Guangxi Zhuang Autonomous Region,, 533000,, Baise,, China.
BMC Neurosci. 2025 Jul 13;26(1):40. doi: 10.1186/s12868-025-00964-6.
To explore the effects of arabinoxylan on the BDNF/TrkB/p-CREB signaling pathway in the prefrontal cortex of post-stroke depressed rats, and to explore its neuronal protective effects through the microbial-gut-brain axis in the regulation of this pathway.
The rat model of post-stroke depression (PSD) was established by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stimulation (CUMS). They were randomly divided into 5 groups (blank control, post-stroke depression, arabinoxylan, fluoxetine hydrochloride, fluoxetine hydrochloride combined arabinoxylan). The rats were treated differently for 28 days according to their grouping. Body mass, sugar and water consumption experiments and open-field experiments were used to evaluate the behavior of rats. The pathological changes were observed by H&E staining. The expression levels of amine neurotransmitters were detected by ELISA. The expression levels of BDNF mRNA and BDNF, TrkB and p-CREB were detected by RT-PCR and Western blot. The analysis of intestinal metagenomics was conducted by 16 S rDNA sequencing.
Compared with the post-stroke depression group, the body weight, activity and sugar water consumption rate of the arabinoxylan group were increased. The expression levels of 5-HT in the prefrontal cortex, colon and serum levels of 5-HT, DA and NE were increased. The expression levels of BDNF mRNA and BDNF, TrkB and P-CREB in the prefrontal cortex were also upregulated. The number of neurons in the prefrontal cortex increased; Colon mucosal injury and inflammatory cell infiltration decreased, the intestinal microbial diversity increased; The relative abundance of probiotics such as bifidobacterium, Christensenia, Dubosiella New York and ruminococcus increased. The relative abundance of Prevotella NK3B31 group was reduced. The level of 5-HT in the prefrontal cortex was negatively correlated with the abundance of Prevotellaceae NK3B31 group.
Arabinoxylan improved depressive-like behavior in rats and its neuroprotective role was achieved by promoting the growth of intestinal probiotics, improving the intestinal barrier, affecting the BDNF/TrkB/p-CREB signaling pathway, and increasing the expression levels of monoamine neurotransmitters 5-HT, DA and NE.
探讨阿拉伯木聚糖对脑卒中后抑郁大鼠前额叶皮质BDNF/TrkB/p-CREB信号通路的影响，并通过微生物-肠道-脑轴调控该通路探讨其神经保护作用。
采用大脑中动脉闭塞（MCAO）联合慢性不可预测轻度刺激（CUMS）建立脑卒中后抑郁（PSD）大鼠模型。将其随机分为5组（空白对照、脑卒中后抑郁、阿拉伯木聚糖、盐酸氟西汀、盐酸氟西汀联合阿拉伯木聚糖）。根据分组对大鼠进行不同处理28天。采用体重、糖水消耗实验和旷场实验评估大鼠行为。通过苏木精-伊红（H&E）染色观察病理变化。采用酶联免疫吸附测定（ELISA）检测胺类神经递质表达水平。采用逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法（Western blot）检测BDNF mRNA及BDNF、TrkB和p-CREB的表达水平。通过16S核糖体DNA测序进行肠道宏基因组学分析。
与脑卒中后抑郁组相比，阿拉伯木聚糖组大鼠体重、活动度及糖水消耗率增加。前额叶皮质5-羟色胺（5-HT）、结肠及血清中5-HT、多巴胺（DA）和去甲肾上腺素（NE）表达水平升高。前额叶皮质BDNF mRNA及BDNF、TrkB和磷酸化环磷腺苷反应元件结合蛋白（P-CREB）表达水平也上调。前额叶皮质神经元数量增加；结肠黏膜损伤及炎性细胞浸润减少，肠道微生物多样性增加；双歧杆菌、克里斯滕森菌、纽约杜波西拉菌和瘤胃球菌等益生菌相对丰度增加。普雷沃菌属NK3B31组相对丰度降低。前额叶皮质5-HT水平与普雷沃菌科NK3B31组丰度呈负相关。
阿拉伯木聚糖改善大鼠抑郁样行为，其神经保护作用通过促进肠道益生菌生长、改善肠道屏障、影响BDNF/TrkB/p-CREB信号通路及增加单胺类神经递质5-HT、DA和NE表达水平实现。
