Vitamin D Ameliorates Doxorubicin-Induced Cognitive Dysfunction via Modulation of the SFRP1/β-Catenin Axis

This study investigated the neuroprotective effects of vitamin D (VD) supplementation in mitigating chemotherapy-induced cognitive dysfunction (CICD) induced by doxorubicin (DOX) in a mouse model. Given the widespread impact of chemotherapy-induced neurotoxicity, the purpose was to explore the potential of VD to alleviate cognitive impairment and its underlying molecular mechanisms. We administered cholecalciferol emulsion (CCE), a VD analog, and assessed its effects on behavior, oxidative stress, inflammation, and neuronal integrity. Our findings demonstrate that CCE treatment significantly improved cognitive function, reduced oxidative stress, and attenuated neuroinflammation in the hippocampus. Furthermore, molecular analysis revealed that VD supplementation modulated the Wnt/β-catenin signaling pathway, notably through the suppression of SFRP1 and activation of PPAR-γ. These results suggest that VD exerts its neuroprotective effects by regulating key signaling pathways involved in neuroprotection, making it a promising candidate for therapeutic strategies to mitigate doxorubicin-induced cognitive decline.

PPAR-γ; SFRP1; chemotherapy-induced cognitive dysfunction; cognitive impairment; doxorubicin; neuroprotection; vitamin D; β-catenin pathway.