J Nutr Biochem. 2025 Oct 13. pii: S0955-2863(25)00307-9. [Epub ahead of print] 110145
BACKGROUND: Motor, visual, and cognitive decline are early signs of dopaminergic system dysfunction (DSD), yet the mechanisms underlying associated visuospatial memory impairment are poorly understood. This study evaluated visuospatial memory in DSD and the neuroprotective effects of vitamins D3 and A.
METHODS: Animals were grouped as NS (control), -D2 (15 mg/kg Haloperidol), -D2+VD (Haloperidol + 800 IU vitamin D3), -D2+VA (Haloperidol + 1000 IU vitamin A), -D2+(VD+VA) (Haloperidol + vitamins D3 and A), and -D2+D2 (Haloperidol + 10 mg/kg Bromocriptine). Visuospatial memory was assessed using the visual water box and Y-maze tests. Brain regions and retina were analyzed for histology, immunohistochemistry, oxidative stress, and ELISA for TNF-α, IL-6, IL-4, IL-13, and dopamine.
RESULTS: DSD induced significant visuospatial memory deficits, decreased SOD, IL-4, and IL-13, and increased TNF-α, IL-6, LDH, MDA, reactive astrocytes, degenerating neurons, and extracellular fibrils. Vitamin D alone was moderately effective, while combined vitamin D and A treatment more effectively regulated IL-6, IL-13, MDA, and reactive astrocytes in the prefrontal cortex and hippocampus. Other parameters were similarly improved by single or combined treatment.
CONCLUSION: Dopaminergic system dysfunctions are linked to visuospatial memory impairment due to increased cytotoxicity, pro-inflammatory cytokines, oxidative stress, neural alterations, and reactive astrocyte expression, leading to reduced dopamine concentration in the PFC, HPC, visual cortex, and retina. Administration of vitamin A and D is more potent in providing a defensive mechanism by downregulating oxidative stress, reactive astrocytes, and their associated proinflammatory cytokines. All of which contribute to the regulation of dopamine levels.
Keywords: Dopaminergic system dysfunction; Inflammatory cytokines; Reactive astrocytes; Vitamin A; Vitamin D3; oxidative stress; visuospatial memory function