Dimethyl fumarate attenuates cadmium-induced neurobehavioural deficits, NF-κB/NLRP3-associated neuroinflammation and synaptic protein alterations in rats.

Cadmium (Cd) exposure is associated with cognitive dysfunction, neuroinflammation and synaptic impairment. This study evaluated whether dimethyl fumarate (DMF) attenuates CdCl₂-induced neurotoxicity in rats and whether protection is associated with reduced NF-κB/NLRP3-associated inflammatory signalling and preservation of synaptic proteins. Male Wistar rats received control, CdCl₂ (5 mg/kg/day), DMF (25 mg/kg/day) or CdCl₂ + DMF treatment orally for 30 days (n = 8/group). CdCl₂ impaired spatial learning, recognition memory, spontaneous alternation and exploratory activity; increased TNF-α, IL-1β and IL-6; enhanced NF-κB p65 expression/phosphorylation and NLRP3, ASC and cleaved caspase-1 and reduced BDNF, synaptophysin, PSD-95 and NMDAR subunits in the hippocampus and prefrontal cortex. DMF significantly attenuated these behavioural and molecular alterations. These findings indicate that DMF reduces CdCl₂-induced neurobehavioural and molecular toxicity in association with suppression of NF-κB/NLRP3-associated inflammatory signalling and preservation of neurotrophic and synaptic protein profiles.