| Summary: | Background: The excessive exposure to silver nanoparticles (Ag-NPs) has raised concerns about their possible risks to the human health. The brain is a highly vulnerable organ to nano-silver harmfulness. The aim of this work was to evaluate the impacts of Ag-NPs exposure on the cerebellar cortex of rats. Methods: Rats were assigned to: Control, vehicle control and Ag-NP-exposed groups (at doses of 10 mg and 30 mg/kg/day). Samples were processed for light and electron microscopy examinations. Immunohistochemical localization of c-Jun N-terminal kinase (JNK), nuclear factor kappa beta (NF-κB) and calbindin D28k (CB) proteins was performed. Analyses of expression of DNA damage inducible transcript 4 (<i>Ddit4</i>), flavin containing monooxygenase 2 (<i>FMO2</i>) and thioredoxin-interacting protein (<i>Txnip</i>) genes were done. Serum levels of inflammatory cytokines were also measured. Results: Ag-NPs enhanced apoptosis as evident by upregulation of <i>Ddit4</i> gene expressions and JNK protein immune expressions. Alterations of redox homeostasis were verified by enhancement of <i>Txnip</i> and <i>FMO2</i> gene expressions, favoring the activation of inflammatory responses by increasing NF-κB protein immune expressions and serum inflammatory mediator levels. Another cytotoxic effect was the reduction of immune expressions of the calcium regulator CB. Conclusion: Ag-NPs exposure provoked biochemical, cellular and molecular changes of rat cerebellar cortex in a dose-dependent manner.
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