Tang Liang, Wang Yan, Gong Xujing, Xiang Ju, Zhang Yan, Xiang Qin, Li Jianming
Department of Basic Biology, Changsha Medical College, Changsha, China.
Center for Neuroscience and Behavior, Changsha Medical College, Changsha, China.
Front Pharmacol. 2023 May 15;14:1182803. doi: 10.3389/fphar.2023.1182803. eCollection 2023.
Insulin has an effect on neurodegenerative diseases. However, the role and mechanism of insulin in vascular dementia (VD) and its underlying mechanism are unknown. In this study, we aimed to investigate the effects and mechanism of insulin on VD. Experimental rats were randomly assigned to control (CK), Sham, VD, and insulin (INS) + VD groups. Insulin was administered by intranasal spray. Cognitive function was evaluated using the Morris's water maze. Nissl's staining and immunohistochemical staining were used to assess morphological alterations. Apoptosis was evaluated using TUNEL-staining. Transcriptome and metabolome analyses were performed to identify differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs), respectively. Insulin significantly improved cognitive and memory functions in VD model rats ( < 0.05). Compared with the VD group, the insulin + VD group exhibited significantly reduced the number of Nissl's bodies numbers, apoptosis level, GFAP-positive cell numbers, apoptosis rates, and p-tau and tau levels in the hippocampal CA1 region ( < 0.05). Transcriptomic analysis found 1,257 and 938 DEGs in the VD vs. CK and insulin + VD vs. VD comparisons, respectively. The DEGs were mainly enriched in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse signaling pathways. In addition, metabolomic analysis identified 1 and 14 DEMs between groups in negative and positive modes, respectively. KEGG pathway analysis indicated that DEGs and DEMs were mostly enriched in metabolic pathway. Insulin could effectively improve cognitive function in VD model rats by downregulating tau and p-tau expression, inhibiting astrocyte inflammation and neuron apoptosis, and regulating genes involved in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse pathways, as well as metabolites involved in metabolic pathway.
胰岛素对神经退行性疾病有影响。然而，胰岛素在血管性痴呆（VD）中的作用及机制尚不清楚。在本研究中，我们旨在探讨胰岛素对VD的影响及机制。将实验大鼠随机分为对照组（CK）、假手术组、VD组和胰岛素（INS）+VD组。通过鼻内喷雾给予胰岛素。使用莫里斯水迷宫评估认知功能。采用尼氏染色和免疫组织化学染色评估形态学改变。使用TUNEL染色评估细胞凋亡。分别进行转录组和代谢组分析以鉴定差异表达基因（DEGs）和差异表达代谢物（DEMs）。胰岛素显著改善了VD模型大鼠的认知和记忆功能（<0.05）。与VD组相比，胰岛素+VD组海马CA1区的尼氏体数量、细胞凋亡水平、GFAP阳性细胞数量、凋亡率以及p-tau和tau水平均显著降低（<0.05）。转录组分析发现，在VD与CK以及胰岛素+VD与VD的比较中，分别有1257个和938个DEGs。这些DEGs主要富集在钙信号传导、cAMP信号传导、轴突导向和谷氨酸能突触信号通路中。此外，代谢组分析在阴性和阳性模式下分别鉴定出组间1个和14个DEMs。KEGG通路分析表明，DEGs和DEMs大多富集在代谢通路中。胰岛素可通过下调tau和p-tau表达、抑制星形胶质细胞炎症和神经元凋亡、调节参与钙信号传导、cAMP信号传导、轴突导向和谷氨酸能突触通路的基因以及参与代谢通路的代谢物，有效改善VD模型大鼠的认知功能。
