J Clin Neurol.  2006 Dec;2(4):252-257. 10.3988/jcn.2006.2.4.252.

1alpha,25-Dihydroxyvitamin D3 Protects Dopaminergic Neurons in Rodent Models of Parkinson's Disease through Inhibition of Microglial Activation

• Kim JS
• Ryu SY
• Yun I
• Kim WJ
• Lee KS
• Park JW
• Kim YI

• KMID: 1980465
• DOI: http://doi.org/10.3988/jcn.2006.2.4.252

Abstract

BACKGROUND
Recent studies have demonstrated the molecular basis of the immunomodulatory and anti-inflammatory activities of 1,25-dihydroxyvitamin D3(1,25-(OH)2D3). This hormone improves behavioral deficits and normalizes the nigral dopamine levels in animal models of Parkinson's disease (PD).
METHODS
We studied whether the administration of 1,25-(OH)2D3 would protect against 6-hydroxydopa (6-OHDA)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, and its potential regulatory effect on microglia activation.
RESULTS
We found that 1,25-(OH)2D3 pretreatment significantly decreased 6-OHDA- and MPTP-induced dopaminergic neuronal loss in the substantia nigra pars compacta by preventing the activation of microglia. This observed neuroprotective effect in MPTP-treated mice that were given 1,25-(OH)2D3 may be attributable to inhibition of proinflammatory cytokine expression.
CONCLUSION
These results suggest that 1,25-(OH)2D3 is a potentially valuable neuroprotective agent; it may therefore be considered for the treatment of pathologic conditions of the central nervous system, such as PD, where inflammation-induced neurodegeneration occurs.

Keyword

Vitamin D; Parkinson's disease; 6-hydroxydopa (6-OHDA); 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Cytokine; Inflammation; Rat; Mouse

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Central Nervous System
Dopamine
Dopaminergic Neurons*
Inflammation
Mice
Microglia
Models, Animal
Neurons
Neuroprotective Agents
Parkinson Disease*
Rats
Rodentia*
Substantia Nigra
Vitamin D
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine
Neuroprotective Agents
Vitamin D

Figure

• 

  Figure 1 Expression of TH-immunoreactive cells and activated microglia in the SNpc. (A) TH-positive cell loss following 6-OHDA injection. (B) Microglia reaction after 6-OHDA injection. (C) TH-positive cell loss after intraperitoneal MPTP injection. (D) Microglia reaction after MPTP injection. Cells represent numbers of immunoreactive cells per section (mean±SD values). *P<0.05 †P<0.01.

• 

  Figure 2 Representative RT-PCR demonstrating the expression of TNFα (A), INFγ (B), and GAPDH (C) mRNAs, and the expression pattern of the TNFα (D) and INFγ (E) mRNA in the SNpc at various times after MPTP intoxication. Data are mean±SEM values (n=3). *P<0.05, Mann-Whitney U test.

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