Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian 361012, China.
Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian 361012, China.
Behav Brain Res. 2024 Feb 26;458:114755. doi: 10.1016/j.bbr.2023.114755. Epub 2023 Nov 8.
This study aimed to find the genes and signaling pathways underlying cuprizone-induced demyelination and cognitive impairments in mice. We used the cuprizone-exposed mice as an animal model of schizophrenia and assessed cognitive function in mice. Total RNA was extracted from mouse brain tissues for RNA sequencing. The DESeq2 R package was utilized to analyze the differentially expressed genes (DEGs). Functional and pathway enrichment analyses were performed simultaneously. We also constructed a protein-protein interaction (PPI) network to screen potential hub genes, and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to validate the screened genes. After 6 weeks of cuprizone treatment, the cognitive function of mice was impaired. Compared to the controls, the cuprizone-exposed mice contained 351 DEGs, including 167 upregulated and 184 downregulated genes. Enrichment analysis showed that the DEGs were enriched in some biological processes involved in demyelination, including the MAPK pathway. Functional pathway analysis revealed that the DEGs were significantly enriched in the PI3K-Akt signaling pathway, which may be associated with cognitive impairments. MBP, IGF1, GFAP, PTPRC, CD14, CD68, ITGB2, LYN, TLR2, TLR4, VAV1, and PLEK were considered as potential hub genes. Except for MBP, all genes were upregulated in the cuprizone models, as verified by qRT-PCR. We suggest that the MAPK and PI3K-Akt signaling pathways may be associated with demyelination and cognitive impairments, respectively. GFAP and IGF-1 expression levels increased in cuprizone-exposed mice, suggesting that astrocytes may play a role in protecting the myelin sheath following treatment with cuprizone.
本研究旨在寻找铜锌诱导的脱髓鞘和认知障碍的小鼠的基因和信号通路。我们使用杯状病毒暴露的小鼠作为精神分裂症的动物模型，并评估了小鼠的认知功能。从小鼠脑组织中提取总 RNA 进行 RNA 测序。使用 DESeq2 R 包分析差异表达基因 (DEGs)。同时进行功能和通路富集分析。我们还构建了蛋白质-蛋白质相互作用 (PPI) 网络来筛选潜在的枢纽基因，并采用定量实时聚合酶链反应 (qRT-PCR) 验证筛选出的基因。在铜锌处理 6 周后，小鼠的认知功能受损。与对照组相比，杯状病毒暴露的小鼠有 351 个差异表达基因，其中 167 个上调，184 个下调。富集分析表明，DEGs 富集在一些与脱髓鞘有关的生物学过程中，包括 MAPK 通路。功能通路分析表明，DEGs 在 PI3K-Akt 信号通路中显著富集，这可能与认知障碍有关。MBP、IGF1、GFAP、PTPRC、CD14、CD68、ITGB2、LYN、TLR2、TLR4、VAV1 和 PLEK 被认为是潜在的枢纽基因。除了 MBP 之外，所有基因在杯状病毒模型中均上调，qRT-PCR 验证了这一点。我们认为 MAPK 和 PI3K-Akt 信号通路可能分别与脱髓鞘和认知障碍有关。GFAP 和 IGF-1 的表达水平在杯状病毒暴露的小鼠中升高，提示星形胶质细胞在铜锌处理后可能在保护髓鞘鞘方面发挥作用。
