Co-exposure to environmental lead and hypertension exacerbates anxiety and depression via mtDNA-mediated cGAS phase separation.

Co-exposure to lead and hypertension in mice significantly worsens anxiety- and depression-like behaviors, with effects linked to cGAS phase separation and astrocyte senescence.

• Why it matters: Understanding the combined neurotoxic effects of environmental lead and hypertension is crucial because these factors often coexist and contribute to mood disorders, yet their joint impact remains poorly understood.
• What they did: The study used a combined exposure model in mice, revealing that co-exposure exacerbates behavioral deficits, promotes cGAS phase separation, and induces astrocyte senescence, which can be alleviated by senolytic treatment and pharmacological interventions targeting mtDNA and biomolecular condensates.
• The result: Findings suggest that mtDNA-dependent cGAS phase separation drives astrocyte senescence and neuropsychiatric dysfunction, highlighting cGAS phase separation as a potential therapeutic target for anxiety and depression caused by environmental lead and hypertension.