1alpha,25-Dihydroxyvitamin D(3) Protects Dopaminergic Neurons in Rodent Models of Parkinson's Disease through Inhibition of Microglial Activation.
BACKGROUND
Recent studies have demonstrated the molecular basis of the immunomodulatory and anti-inflammatory activities of 1,25-dihydroxyvitamin D(3)(1,25-(OH)(2)D(3)). 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)(2)D(3) 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)(2)D(3) 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)(2)D(3) may be attributable to inhibition of proinflammatory cytokine expression.


CONCLUSIONS
These results suggest that 1,25-(OH)(2)D(3) 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.
Kim
Joong-Seok
JS
Department of Neurology, The Catholic University of Korea, Seoul, Korea.
Ryu
Sun-Young
SY
Yun
Injin
I
Kim
Woo-Jun
WJ
Lee
Kwang-Soo
KS
Park
Jeong-Wook
JW
Kim
Yeong-In
YI
Pharmacol Biochem Behav. 2004 May;78(1):143-53
15159144
Acta Neurobiol Exp (Wars). 2003;63(2):117-26
12926538
Glia. 1998 Mar;22(3):282-94
9482214
Nature. 1996 Mar 21;380(6571):252-5
8637574
Brain Res Mol Brain Res. 2002 Dec;108(1-2):143-6
12480187
J Neurosci Res. 2000 Nov 1;62(3):374-82
11054806
J Pharmacol Exp Ther. 2003 Jan;304(1):1-7
12490568
J Neural Transm (Vienna). 1996;103(8-9):987-1041
9013391
Neurology. 1988 Aug;38(8):1285-91
3399080
Curr Pharm Des. 2005;11(8):999-1016
15777250
Curr Drug Targets Inflamm Allergy. 2004 Dec;3(4):377-93
15584887
Neuroreport. 1996 Sep 2;7(13):2171-5
8930983