Synergistic Action of Vitamin D3 and A Protects Motor Activity by Regulating Reactive Astrocytes, Inflammatory Cytokines, and Dopaminergic Activity in the Corticobasal Loop of a Mice Model of Extrapyramidal Syndrome

Abstract

Background: Extrapyramidal syndromes (EPS) represent neurological side effects of antipsychotic medications, characterized by motor disturbances. While previous studies have indicated the neuroprotective effects of vitamin D and A against EPS, the underlying mechanisms of this protection remain unclear.Methods: Twenty-four adult male mice were categorized into four groups: positive and negative control groups, one receiving a dopamine antagonist, and the other receiving both a dopamine antagonist and vitamins D and A. Sections of the corticobasal loop, specifically the motor cortex (M1) and basal nuclei (CPu), were prepared for Immunohistochemistry (IHC) and stained with Glial Fibrillary Acidic Protein (GFAP) to visualize active astrocytes. ELISA assays for TNF-α, IL-6, IL-4, IL-13, and dopamine levels were performed on homogenized brain sections.Results: The EPS group exhibited a significant increase in TNF-α and IL-6 levels in M1 and CPu. Treatment with dopamine agonists and vitamin D/A resulted in significant reductions in IL-6 levels. Only the Vitamin D/A group showed a significant decline in TNF-α. The EPS group recorded significant decreases in IL-4 and IL-13, with IL-13 significantly elevated in the dopamine agonist and Vitamin D/A groups. IL-4 was notably increased in the Vitamin D/A groups. Dopamine concentration significantly declined in the EPS group, with improvements observed in the groups treated with dopamine agonists, vitamin D, and A. Reactive astrocytes were significantly expressed in the M1 and CPu of the EPS group but poorly expressed in other regions.Conclusions: EPS is linked to astrocyte activation, an upsurge in pro-inflammatory cytokines, a decline in anti-inflammatory cytokines, and dopamine in the corticobasal loop. Administration of vitamin D3 and A was found to exert its effects by suppressing pro-inflammatory cytokines and repressing anti-inflammatory cytokines associated with astrocyte activation.