ArticleEnvironmental analysis, health and toxicology2025
Purinergic system dysregulation and depression: The neuroinflammatory impact of silica nanoparticles.
Article in Environmental analysis, health and toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Major depressive disorder (MDD) is a neuropsychiatric condition linked to neurotransmitter imbalances, neuroinflammation, and purinergic signaling dysregulation. Emerging evidence suggests that environmental pollutants, such as silica nanoparticles (SiNPs), contribute to neuroinflammatory responses and depressive-like behaviors, though the mechanisms remain unclear. This study investigates the effects of repeated SiNP exposure on depressive-like behaviors and purinergic signaling in the hippocampus of adult male rats. Thirty-six Wistar rats were divided into three groups (control, low-dose SiNP, high-dose SiNP) and received intraperitoneal injections for 28 days. Depressive-like behaviors were assessed using the Forced Swimming Test (FST) and Tail Suspension Test (TST), while the enzymatic activities of ectonucleotidases (E-NTPDase, E-NPP, and ecto-5'-nucleotidase) and ATPase function were measured in hippocampal tissue. Gene expression of purinergic receptors (A2A, P2X7, P2Y2) and ectonucleotidases (CD73, NTPDase 1-3) was analyzed via RT-qPCR, with immunohistochemistry and immunofluorescence assessing CD73 and CD90 protein levels. SiNP exposure significantly increased immobility time in both behavioral tests, indicating depressive-like behavior. It also upregulated ectonucleotidase activity, purinergic receptors (A2A, P2X7, P2Y2), and CD73/CD90 expression, while disrupting ATPase function by decreasing both Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities. These findings suggest that SiNPs induce depressive-like behavior through purinergic pathway dysregulation, promoting neuroinflammation and neurotransmission alterations. Further studies are needed to explore purinergic signaling as a potential therapeutic target in depression.
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