Dati L M, Ulrich H, Real C C, Feng Z P, Sun H S, Britto L R
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil.
Department of Biochemistry, Institute of Chemistry, University of São Paulo, Brazil.
Neuroscience. 2017 Jul 25;356:176-181. doi: 10.1016/j.neuroscience.2017.05.013. Epub 2017 May 17.
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-hydroxy-dopamine 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 6-hydroxy-dopamine model of Parkinson's disease, possibly by its non-specific blocking effect upon TRPM7 channels.
香芹酚是一种单萜类化合物，在包括缺血、癫痫和创伤性神经元损伤在内的多种神经退行性疾病动物模型中，已被证明与神经保护作用有关。在本研究中，我们研究了香芹酚腹腔注射对小鼠单侧纹状体内注射6-羟基多巴胺诱导的神经退行性变的影响。我们还使用圆筒实验评估香芹酚在帕金森病模型中的行为学效应，并通过免疫印迹法评估香芹酚的主要靶点之一caspase-3和瞬时受体电位M型7通道（TRPM7）的水平。行为学测试显示，香芹酚在很大程度上减少了单侧6-羟基多巴胺诱导的前肢不对称使用。香芹酚显著减少了模型典型的黑质和纹状体内酪氨酸羟化酶免疫染色的丢失。酪氨酸羟化酶的免疫印迹证实了这一效应。毒素注射后caspase-3水平非常高，但香芹酚似乎将其降低至对照水平。最后，免疫印迹观察到的TRPM7在6-羟基多巴胺注射后增加，表明该阳离子通道参与了随后的神经退行性过程。目前的数据表明，香芹酚在帕金森病的6-羟基多巴胺模型中具有显著的神经保护作用，可能是通过其对TRPM7通道的非特异性阻断作用实现的。
