Objective: The study investigated the impacts of VD3 on behavioural indices, dopamine metabolism, DA transport, BDNF, corticostriatal neural activities and the possible mechanism of action of VD3 in PD and dyskinetic mice

Background: L-DOPA is the gold standard for the management of PD. Although it provides symptomatic motor relief, this often wears off overtime. Also, L-DOPA therapy is unable to slow down the disease progression, and debilitating motor defect such as dyskinesia often develops after its prolonged use. Vitamin-D Receptors are highly abundant in the nigrostriatal tract, an area primarily affected in PD, suggesting an intricate role of Vitamin D in brain development and function in health and diseases especially neurodegenerative disorders

Method: C57BL6 mice were induced with PD by stereotaxic injection of 6-OHDA into the striatum. Mice were divided into 5 groups: Control, PD, PD/VD3 (30mg/kg for 21days), PD/L-DOPA (10mg/kg), & PD/VD3+L-DOPA. After treatments, motor behavioural indices were conducted. Dyskinesia was induced by chronic administration of 20mg/kg L-DOPA on PD mice for 10days. Mice were divided into 4 groups: Control, dyskinesia, dyskinesia/VD3 (30mg/kg), dyskinesia/Amantadine (40mg/kg). Response of mice to L-DOPA-induced abnormal involuntary movements following interventions with VD3 or Amantadine was recorded. in-vivo neural recording was taken from corticostriatal axis of the brain. Then, the striatum was processed for quantitative expression of DA metabolic enzymes, DA transporter, Brain-derived neurotrophic factor, BAX, CD11β, IL-1β, p47phox using western immunoblotting

Results: VD3 attenuated motor deficits PD and AIMs in dyskinetic mice. It improved dopaminergic neurotransmission by modulating the activities of DA metabolic enzymes, transporter and BDNF in PD but had no effect on metabolic enzymes in dyskinesia. VD3 improved subthreshold neural activities in PD and dampened excessive neuronal activity in dyskinetic mice. VD3 exerted neuroprotective effect by downregulating microglia activation, oxidative stress & neuro-inflammation in both conditions

Conclusion: Cholecalciferol has both anti-parkinsonian and anti-dyskinetic effects. Its neuroprotective effects suggest that, apart from slowing down the progression of PD, it may also reduce L-DOPA dosage thereby reducing the short comings of L-DOPA therapy in the management of PD

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cholecalciferol-vd3-attenuated-motor-deficits-and-dyskinesia-in-hemi-parkinsonian-mice-behavioural-biochemical-electrophysiological-implications/