ArticleBrain and behavior2026
Combined Vitamin D and Resveratrol Treatment Attenuates Motor Deficits and Neurodegeneration in a 6-OHDA Mouse Model of Parkinson's Disease in Male Mice: A Focus on Sirt1 and Lingo-1 Pathways in the Ventral Tegmental Area.
Article in Brain and behavior, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundParkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration, leading to severe motor impairments. Lingo-1 negatively regulates neuronal survival, while Sirtuin-1 (Sirt1) supports mitochondrial function and oxidative stress resistance. Given the neuroprotective properties of Vitamin D3 (VitD3) and resveratrol, this study examined whether their combined administration could modulate Sirt1 and Lingo-1 expression and attenuate neurodegeneration in a 6-hydroxydopamine (6-OHDA) model of PD.
methodsMale Swiss mice were assigned to six groups: Control, Sham, 6-OHDA, 6-OHDA + Resveratrol (5 mg/kg), 6-OHDA + VitD3 (0.1 µg/kg), and 6-OHDA + Res + VitD3. Behavioral performance was evaluated using open field, footprint, wire grip, and rotarod tests. Neuronal integrity within the ventral tegmental area (VTA) was assessed via Nissl staining, while Sirt1 and Lingo-1 gene expression levels were quantified by RT-qPCR.
results6-OHDA lesioning produced marked reductions in locomotor activity, grip strength, and rotarod performance, accompanied by significant neuronal loss in the VTA and dysregulated Sirt1/Lingo-1 expression. Treatment with VitD3 or resveratrol alone partially improved motor performance and reduced neuronal loss, whereas the combination therapy produced the most pronounced neuroprotection. Co-administration of VitD3 and resveratrol normalized Sirt1 expression, suppressed Lingo-1 upregulation, and preserved neuronal morphology in the VTA.
conclusionsCombined treatment with VitD3 and resveratrol mitigates motor deficits and neurodegeneration in 6-OHDA-lesioned mice which was associated with activation of Sirt1 and suppression of Lingo-1. The results suggest the therapeutic potential of targeting the Sirt1 and Lingo-1 signaling pathways via nutraceutical interventions as a disease-modifying strategy in PD.
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