Curcumin attenuates acrylamide-induced cerebellar neurofilament accumulation, BDNF decline and motor dysfunction.

Acrylamide (ACR), a well-established neurotoxicant in humans, is commonly encountered in daily life. Previous studies have implicated cerebellar injury in ACR-induced neurotoxicity. Curcumin, a polyphenolic compound with potent neuroprotective properties, has shown protective effects in maintaining cerebellar function by suppressing oxidative stress. This study aimed to determine whether curcumin could alleviate ACR-induced motor dysfunction and cerebellar injury in rats. Administration of ACR at a dose of 10 mg/kg/day for 7 weeks induced mild gait abnormality, impaired motor coordination and balance, and significant cerebellar neuronal loss. These alterations were accompanied by oxidative stress, neurofilament accumulation and microtubule dynamic instability. ACR increased cerebellar malondialdehyde (MDA) level, reduced glutathione (GSH) level and activities of total superoxide dismutase (T-SOD) and catalase (CAT). At the molecular level, ACR exposure increased the expression of neurofilament light chain (NF-L) and reduced the levels of phosphorylated cAMP response element-binding protein (P-CREB) and brain-derived neurotrophic factor (BDNF). ACR increased tau phosphorylation and decreased acetylated α-tubulin. Curcumin intervention partially alleviated ACR-induced motor dysfunction and cerebellar cytoskeletal injury, attenuated oxidative stress, reduced NF-L accumulation, increased ERK1/2 and Akt phosphorylation, and elevated P-CREB and BDNF levels. However, curcumin had limited effects on cerebellar tau phosphorylation and microtubule instability. These results provide novel insights into the protective effects of curcumin against ACR-induced cerebellar toxicity and highlight its therapeutic potential as a protective intervention against ACR-induced neurotoxicity.