神经炎症
免疫系统
促炎细胞因子
CD8型
小胶质细胞
T细胞
生物
流式细胞术
内分泌学
细胞毒性T细胞
内科学
海马结构
断奶
免疫学
炎症
医学
体外
生物化学
作者
Michael J. Butler,Shouvonik Sengupta,Stephanie Muscat,Stephanie A. Amici,Rebecca G. Biltz,Nicholas P. Deems,Piyush Dravid,Sabrina Alfonso-Mackey,Haanya Ijaz,Menaz N. Bettes,Jonathan P. Godbout,Amit Kapoor,Mireia Guerau-de-Arellano,Ruth M. Barrientos
标识
DOI:10.1016/j.bbi.2023.02.003
摘要
We have previously shown that short-term (3-day) high fat diet (HFD) consumption induces a neuroinflammatory response and subsequent impairment of long-term memory in aged, but not young adult, male rats. However, the immune cell phenotypes driving this proinflammatory response are not well understood. Previously, we showed that microglia isolated from young and aged rats fed a HFD express similar levels of priming and proinflammatory transcripts, suggesting that additional factors may drive the exaggerated neuroinflammatory response selectively observed in aged HFD-fed rats. It is established that T cells infiltrate both the young and especially the aged central nervous system (CNS) and contribute to immune surveillance of the parenchyma. Thus, we investigated the modulating role of short-term HFD on T cell presence in the CNS in aged rats using bulk RNA sequencing and flow cytometry. RNA sequencing results indicate that aging and HFD altered the expression of genes and signaling pathways associated with T cell signaling, immune cell trafficking, and neuroinflammation. Moreover, flow cytometry data showed that aging alone increased CD4+ and CD8+ T cell presence in the brain and that CD8+, but not CD4+, T cells were further increased in aged rats fed a HFD. Based on these data, we selectively depleted circulating CD8+ T cells via an intravenous injection of an anti-CD8 antibody in aged rats prior to 3 days of HFD to infer the functional role these cells may be playing in long-term memory and neuroinflammation. Results indicate that peripheral depletion of CD8+ T cells lowered hippocampal cytokine levels and prevented the HFD-induced i) increase in brain CD8+ T cells, ii) memory impairment, and iii) alterations in pre- and post-synaptic structures in the hippocampus and amygdala. Together, these data indicate a substantial role for CD8+ T cells in mediating diet-induced memory impairments in aged male rats.
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