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. 2008 Jul 19;24(3):133–142. doi: 10.1007/s12264-008-1225-9

Triptolide protects against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats: Implication for immunosuppressive therapy in Parkinson’s disease

Jun-Peng Gao 1, Shan Sun 1, Wen-Wei Li 1, Yi-Ping Chen 1, Ding-Fang Cai 1,✉
PMCID: PMC5552541  PMID: 18500385

Abstract

Objective

Neuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson’s disease (PD). The present study was undertaken to evaluate the activation profile of microglia in 1-methyl-4-phenyl pyridinium (MPP+)-induced hemiparkinsonian rats. Triptolide, a potent immunosuppressant and microglia inhibitor, was then examined for its efficacy in protecting dopaminergic neurons from injury and ameliorating behavioral disabilities induced by MPP+.

Methods

The rat model of PD was established by intranigral microinjection of MPP+. At baseline and on day 1, 3, 7, 14, 21 following MPP+ injection, the degree of microglial activation was examined by detecting the immunodensity of OX-42 (microglia marker) in the substantia nigra (SN). The number of viable dopaminergic neurons was determined by measuring tyrosine hydroxylase (TH) positive neurons in the SN. Behavioral performances were evaluated by counting the number of rotations induced by apomorphine, calculating scores of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry.

Results

Intranigral injection of MPP+ resulted in robust activation of microglia, progressive depletion of dopaminergic neurons, and ongoing aggravation of behavioral disabilities in rats. Triptolide significantly inhibited microglial activation, partially prevented dopaminergic cells from death and improved behavioral performances.

Conclusion

These data demonstrated for the first time a neuroprotective effect of triptolide on dopaminergic neurons in MPP+-induced hemiparkinsonian rats. The protective effect of triptolide may, at least partially, be related to the inhibition of MPP+-induced microglial activation. Our results lend strong support to the use of immunosuppressive agents in the management of PD.

Keywords: Parkinson’s disease, triptolide, microglia, neurons

Footnotes

These two authors contributed equally to this work.

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