Astrocyte-derived extracellular vesicular NFIA mediates obesity-associated cognitive impairment

Quick Facts

  • Publication title: Astrocyte-derived extracellular vesicular NFIA mediates obesity-associated cognitive impairment
  • Journal: J Neuroinflammation
  • Year: 2025
  • DOI: 10.1186/s12974-025-03473-9
  • PMID/PMCID: 40448146; PMC12125936

Research overview

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.

Key findings

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.

Study design

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 Role

Echo Biotech contributed EV isolation and purification, EV characterization, EV proteomics.

Related platforms: Exoomics®

Related services and capabilities: Tissue EV Isolation & Purification, EV Basic Characterization (TEM/NTA/WB), EV Proteomics

References

Original publication: 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.