J Korean Neurol Assoc.  2005 Jun;23(3):368-373.

The Effect of 1, 25-Dihydroxyvitamin D3 on Dopaminergic Neurons and Microglial Activation in Parkinsonian Rat Model Induced by 6-Hydroxydopamine

• Ryu SY
• Kim JS
• Choi YB
• Han SR
• Park JW
• Park SK
• Kim YI

Abstract

BACKGROUND
Recent studies have shown increasing evidence for microglial activation in neuronal degeneration in Parkinson's disease (PD), although the cause of PD remains unclear. Recent studies have also shown that 1alpha, 25-dihydroxyvitamin D3 (vitamin D3) exert neuroprotective effects by inducing an increased expression of neurotrophic factors, suggesting the possibility of vitamin D3 for the treatment of PD and other neurodegenerative diseases. The purpose of this study was to investigate the effect of vitamin D3 on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and microglial activation in adult rats. METHODS: Adult male Sprague-Dawley rats were subcutaneously injected with vitamin D3 or 0.1% ethanol for seven consecutive days and then infused unilaterally with 6-OHDA in the medial forebrain bundle. After 7 days of injection with 6-OHDA, the substantia nigra was examined by immunohistochemistry. RESULTS: The number of tyrosine hydroxylase (TH)-positive neurons in the lesioned substantia nigra pars compacta of vitamin D3 and ethanol groups was 84.8 +/- 18.84 and 52.6 +/- 13.23, respectively, fewer than that of the contralateral side (122.35 +/- 9.79 and 123.81 +/- 12.11, respectively) (P<0.05). The vitamin D3 group showed significantly higher numbers of the TH-positive neurons than that of the ethanol group (P<0.05). CD11b-positive microglial immunoreactivity was stronger in the lesion side than that of the normal side, and it was much weaker in the vitamin D3 group than that of the ethanol group (P<0.05). CONCLUSIONS: These results indicate that vitamin D3 protects dopaminergic neurons from the neuronal injury induced by 6-OHDA, possibly by the mechanism involving microglial activation.

Keyword

Vitamin D3; Microglia; Parkinson's disease; 6-hydroxydopamine

MeSH Terms

Adult
Animals
Cholecalciferol
Dopaminergic Neurons*
Ethanol
Humans
Immunohistochemistry
Male
Medial Forebrain Bundle
Microglia
Models, Animal*
Nerve Growth Factors
Neurodegenerative Diseases
Neurons
Neuroprotective Agents
Oxidopamine*
Parkinson Disease
Rats*
Rats, Sprague-Dawley
Substantia Nigra
Tyrosine 3-Monooxygenase
Cholecalciferol
Ethanol
Nerve Growth Factors
Neuroprotective Agents
Oxidopamine
Tyrosine 3-Monooxygenase