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PFOA induces apoptosis in primary cortical neurons via GLS2 inhibition-mediated ROS accumulation
Cixia Li1, Yu Fang1, Junying Zhang2
1College of Life Science and Technology, Henan Medical University, Xinxiang, Henan 453003, PR China.
Ecotoxicology and Environmental Safety
|July 18, 2026
Summary
Perfluorooctanoic acid (PFOA) exposure harms cortical neurons by increasing oxidative stress and apoptosis. This study reveals PFOA suppresses GLS2, a key gene, leading to neurotoxicity and suggesting GLS2 as a therapeutic target.
Area of Science:
- Neuroscience
- Environmental Toxicology
- Molecular Biology
Background:
- Perfluorooctanoic acid (PFOA) is a persistent environmental pollutant with known bioaccumulative properties.
- Increasing health concerns surround PFOA due to its potential neurotoxicity.
- The precise mechanisms underlying PFOA's adverse effects on cortical neurons are not well understood.
Purpose of the Study:
- To investigate the neurotoxic effects of PFOA on primary cortical neurons.
- To elucidate the molecular mechanisms, including oxidative stress and apoptosis pathways, involved in PFOA-induced neurotoxicity.
- To identify potential molecular targets for mitigating PFOA's harmful effects on neurons.
Main Methods:
- Primary mouse cortical neurons were exposed to varying concentrations of PFOA.
- Assessed intracellular reactive oxygen species (ROS) levels, cell viability, and apoptosis.
- Examined neuronal morphology, NF-κB activation, and nuclear translocation via immunofluorescence.
- Utilized Western blotting to analyze protein expression (NF-κB, p-NF-κB, GLS2, Bax, Bcl-2, Caspase-3).
- Performed transcriptomic analysis on GEO dataset GSE254408 and intracellular glutamate assays.
Main Results:
- PFOA exposure reduced neurite length, branch number, and soma size in cortical neurons.
- Dose-dependent increases in ROS accumulation, NF-κB activation, and apoptosis were observed with PFOA treatment.
- Transcriptomic analysis revealed significant downregulation of GLS2, a gene crucial for neuronal homeostasis.
- PFOA treatment decreased intracellular glutamate levels and altered the expression of apoptosis-related proteins (Bax, Bcl-2, Caspase-3).
- Overexpression of GLS2 partially protected neurons against PFOA-induced ROS and apoptosis.
Conclusions:
- PFOA exposure induces neurotoxicity in cortical neurons, characterized by oxidative stress and apoptosis.
- Suppression of GLS2 by PFOA contributes to neuronal damage and apoptosis.
- GLS2 emerges as a potential molecular target for addressing PFOA-induced neurotoxicity.
- These findings provide mechanistic insights into PFOA's neurotoxic effects, relevant for hazard identification and therapeutic strategies.
