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

Co-exposure to environmental lead and hypertension significantly worsens anxiety and depression in mice, with a 2.5-fold increase in behavioral deficits compared to single exposures.

• Why it matters: Understanding the combined neurotoxic effects of heavy metals and hypertension is crucial because these conditions often coexist and contribute to mental health disorders, yet their interaction remains poorly understood.
• What they did: Researchers used a mouse model with co-exposure to lead and angiotensin II, employing pharmacological and molecular techniques to investigate cellular and molecular changes, including cGAS phase separation and mitochondrial DNA dynamics.
• The result: Findings reveal that co-exposure promotes cGAS phase separation mediated by mitochondrial DNA, leading to astrocyte senescence and neuropsychiatric symptoms, which can be mitigated by senolytics and inhibitors of cGAS phase separation.