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Tripchlorolide protects against MPTP‐induced neurotoxicity in C57BL/6 mice
Author(s) -
Hong Zhen,
Wang Gang,
Gu Jing,
Pan Jing,
Bai Li,
Zhang Shi,
Chen ShengDi
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05766.x
Subject(s) - mptp , substantia nigra , pars compacta , striatum , neurotoxicity , tyrosine hydroxylase , dopaminergic , neuroprotection , dopamine , chemistry , parkinson's disease , pharmacology , neurotoxin , medicine , endocrinology , toxicity , disease
Many current studies of Parkinson's disease (PD) suggest that inflammation is involved in the neurodegenerative process. Tripchlorolide (TW397), a traditional Chinese herbal compound with anti‐inflammatory and immunosuppressive properties, has been shown to protect dopaminergic neurons against, and restore their function after, the neurotoxicity induced by 1‐methyl‐4‐phenylpyridinium ions in vitro . This study was designed to investigate the effect of TW397 in vivo in the PD model of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐lesioned C57BL/6 mice. In the animals that received vehicle‐only (i.e., no TW397) treatment with MPTP i.p. injection, the survival ratios of tyrosine hydroxylase‐immunoreactive (TH‐IR) neurons in the substantia nigra pars compacta and TH‐IR fibres in the striatum were only 59 and 13%, respectively, compared with the normal controls. Intriguingly, in conjunction with MPTP, treatment with TW397, 1 µg/kg for 16 days, once per day, dramatically improved the survival rate of the TH‐IR neurons and TH‐IR fibres to 80 and 43% of the control. The treatment with TW397 also significantly improved the level of dopamine in the substantia nigra and striatum to 157 and 191%, respectively, of the MPTP‐ plus vehicle‐treated group. In addition, in MPTP‐treated animals the rota‐rod performances of those treated with 0.5 or 1 µg/kg TW397 were significantly improved, by ∼2‐ and 3‐fold, respectively, relative to vehicle‐treated animals. The neuroprotective effect of TW397 was coincident with an attenuated astroglial response within the striatum. These data demonstrate a neuroprotective action of TW397 in vivo against MPTP toxicity, with important implications for the treatment of PD.