CARVACROL PROMOTES NEUROPROTECTION IN THE MOUSE HEMIPARKINSONIAN MODEL

被引:48
作者
Dati, L. M. [1 ]
Ulrich, H. [2 ]
Real, C. C. [1 ]
Feng, Z. P. [3 ]
Sun, H. S. [3 ,4 ]
Britto, L. R. [1 ]
机构
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo, SP, Brazil
[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, Brazil
[3] Univ Toronto, Fac Med, Dept Physiol, Toronto, ON, Canada
[4] Univ Toronto, Fac Med, Dept Surg, Toronto, ON, Canada
基金
巴西圣保罗研究基金会; 加拿大自然科学与工程研究理事会;
关键词
carvacrol; dopamine; neuroprotection; TRP channels; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; TRPM7; CHANNEL; ION CHANNELS; CELL-DEATH; AUTOPHAGY; ISCHEMIA; STRESS; INJURY; BRAIN;
D O I
10.1016/j.neuroscience.2017.05.013
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Carvacrol is a monoterpene that has been linked to neuroprotection in several animal models of neurodegeneration, including ischemia, epilepsy and traumatic neuronal injury. In this study, we investigated the effects of carvacrol (i.p.) upon the neurodegeneration induced by 6-hydroxydopamine unilateral intrastriatal injections in mice. We have also used the cylinder test to assess the behavioral effects of carvacrol in that model of Parkinson's disease, and immunoblots to evaluate the levels of caspase-3 and TRPM7, one of major targets of carvacrol. Behavioral testing revealed that carvacrol largely reduced the asymmetrical use of the forelimbs induced by unilateral 6-hydroxy-dopamine. Carvacrol dramatically reduced the loss of tyrosine hydroxylase immunostaining both in the substantia nigra and in the striatum that are typical of the model. Immunoblots for tyrosine hydroxylase confirmed this effect. Caspase-3 levels were very high after toxin injections, but carvacrol appeared to reduce them to control levels. Finally, TRPM7, observed by immunoblots, increased after 6-hydroxy-dopamine, suggesting the involvement of this cation channel in the ensuing neurodegenerative process. The present data suggest that carvacrol promotes a marked neuroprotection in the 6hydroxy-dopamine model of Parkinson's disease, possibly by its non-specific blocking effect upon TRPM7 channels. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:176 / 181
页数:6
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