Green‐Synthesized Silver Nanoparticles Improve Cognitive Function and Modulate Nrf2/HO‐1–BDNF‐Related Gene Expression in Experimental Chronic Toxoplasmosis
Mojtaba Khaksarian, Amal Khudair Khalaf, Saeedeh Shojaee, Pegah Shakib, Amir Javadi Mamaghani, Erfan Babaeinejad, Hossein MahmoudvandBackground and Aims
This study aimed to evaluate the neuroprotective effects of silver nanoparticles (AgNPs) green‐synthesized using the ethanolic extract of Muscari neglectum against Toxoplasma gondii ‐induced cognitive impairment and to explore the underlying Nrf2/BDNF and oxidative stress–related mechanisms.
Methods
Chronic toxoplasmosis was experimentally induced in mice using the Tehran strain of T. gondii. Forty‐eight mice were randomly allocated into six experimental groups, including a noninfected control group, an infected untreated control group, and four treatment groups receiving pyrimethamine (PYM, 20 mg/kg), donepezil (DON, 2 mg/kg), AgNPs (10 mg/kg), or AgNPs (20 mg/kg). Spatial learning and memory capabilities were assessed using the Morris water maze test. Post‐treatment, brain cyst number and size were determined via microscopic examination. Additionally, quantitative real‐time PCR was employed to evaluate the expression levels of genes associated with oxidative stress and neuroprotection, including brain‐derived neurotrophic factor ( Bdnf ), NADPH oxidase 2 ( Nox2 ), superoxide dismutase 2 ( Sod2 ), catalase ( Cat ), glutathione peroxidase 1 ( Gpx1 ), nuclear factor erythroid 2–related factor 2 ( Nrf2 ), and heme oxygenase‐1 ( Hmox1 ).
Results
Treatment with AgNP resulted in a significant, dose‐dependent improvement in behavioral performance, evidenced by reduced escape latency and enhanced exploration of the target quadrant ( p < 0.001). Moreover, AgNP administration markedly decreased both the number and size of brain Toxoplasma cysts, with the 20 mg/kg dose demonstrating superior efficacy compared to PYM ( p < 0.01). Molecular analyses indicated significant upregulation of Nrf2, Hmox1, Bdnf, Sod2, Cat , and Gpx1 , accompanied by downregulation of Nox2 expression in mice treated with AgNP ( p < 0.001).
Conclusion
These findings suggest that green‐synthesized AgNP exert significant, dose‐dependent antiparasitic and neuroprotective effects in the context of chronic toxoplasmosis. AgNP notably reduced brain cyst burden, enhanced spatial learning and memory, and normalized oxidative stress‐related gene expression. Importantly, AgNP exhibited greater efficacy than both PYM and DON, indicating their potential as a promising therapeutic approach for neurotoxoplasmosis.