星形胶质细胞衍生EV NFIA介导肥胖相关的认知障碍
核心信息
- 论文英文标题: Astrocyte-derived extracellular vesicular NFIA mediates obesity-associated cognitive impairment
- 期刊: J Neuroinflammation
- 发表年份: 2025
- DOI: 10.1186/s12974-025-03473-9
- PMID/PMCID: 40448146; PMC12125936
研究概览
Using comprehensive proteomic sequencing of brain-derived EVs, we identified NFIA as a potentially candidate protein. The mechanistic insight may provide potential therapeutic targets for addressing obesity-related cognitive decline.
核心发现
Following 16 weeks of HFD feeding, obese mice exhibited significant cognitive impairment, which was significantly alleviated by GW4869 administration through inhibition of ceramide-dependent EVs secretion.
Proteomic analysis revealed a marked upregulation of NFIA protein in brain-derived EVs from obese mice, with astrocytes identified as the predominant cellular origin.
ADEVs containing NFIA has been found to specifically accumulated in the hippocampal neurons both in vivo and in vitro.
As expected, ADEVs isolated from high glucose-treated primary astrocytes induced substantial cognitive decline in healthy adult mice and caused synaptic injury in primary cultured neurons.
研究设计
We established an obese mouse model by feeding mice a 60% high-fat diet (HFD) and assessed cognitive function through a series of behavioral tests.
To investigate the role of extracellular vesicles (EVs), we inhibited EVs secretion by intraperitoneally administering GW4869, a neutral sphingomyelinase-2 (nSMase2) inhibitor, to 12-week HFD-fed male mice.
Using comprehensive proteomic sequencing of brain-derived EVs, we identified NFIA as a potentially candidate protein.
Echo Biotech 角色
脑组织外泌体分离鉴定&蛋白质组学
关联平台: Exoomics®
关联服务与能力: Tissue EV Isolation & Purification, EV Basic Characterization (TEM/NTA/WB), EV Proteomics
关联产品或试剂: 无明确产品引用
参考文献
原始论文: Astrocyte-derived extracellular vesicular NFIA mediates obesity-associated cognitive impairment Journal of neuroinflammation. 2025. DOI: 10.1186/s12974-025-03473-9. PMID/PMCID: 40448146; PMC12125936.