Green-Synthesized Silver Nanoparticles Improve Cognitive Function and Modulate Nrf2/HO-1-BDNF-Related Gene Expression in Experimental Chronic Toxoplasmosis.
5 affiliations
- 1Razi Herbal Medicines Research Center Lorestan University of Medical Sciences Khorramabad Iran lums.ac.ir.
- 2Department of Microbiology College of Medicine University of Thi-Qar Nasiriyah Iraq utq.edu.iq.
- 3Department of Medical Parasitology Tehran University of Medical Sciences Tehran Iran tums.ac.ir.
- 4Student Research Committee Lorestan University of Medical Sciences Khorramabad Iran lums.ac.ir.
- 5Hepatitis Research Center Lorestan University of Medical Sciences Khorramabad Iran lums.ac.ir.
Abstract
Background 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.
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BibTeX
@article{khaksarian2026greensynthesized,
title = {{Green-Synthesized Silver Nanoparticles Improve Cognitive Function and Modulate Nrf2/HO-1-BDNF-Related Gene Expression in Experimental Chronic Toxoplasmosis.}},
author = {Mojtaba Khaksarian and Amal Khudair Khalaf and Saeedeh Shojaee and Pegah Shakib and Amir Javadi Mamaghani and Erfan Babaeinejad and Hossein Mahmoudvand},
journal = {Journal of tropical medicine},
year = {2026},
month = oct,
doi = {10.1155/jotm/6264261},
url = {https://europepmc.org/article/MED/42928771},
note = {CC BY},
}
RIS
TY - JOUR
TI - Green-Synthesized Silver Nanoparticles Improve Cognitive Function and Modulate Nrf2/HO-1-BDNF-Related Gene Expression in Experimental Chronic Toxoplasmosis.
AU - Mojtaba Khaksarian
AU - Amal Khudair Khalaf
AU - Saeedeh Shojaee
AU - Pegah Shakib
AU - Amir Javadi Mamaghani
AU - Erfan Babaeinejad
AU - Hossein Mahmoudvand
PY - 2026
DA - 2026/10/25
JO - Journal of tropical medicine
DO - 10.1155/jotm/6264261
UR - https://europepmc.org/article/MED/42928771
AB - Background 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.
SN - 1687-9686
SN - 1687-9694
ER -