The present study examined whether crosstalk between cannabinoid (CB) and transient potential receptor vanilloid type 1 (TRPV1) could contribute to the survival of nigrostriatal dopamine neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). MPTP induced a significant loss of nigrostriatal dopamine neurons and glial activation in the substantia nigra (SN) and striatum (STR) as visualized by tyrosine hydroxylase (TH) or macrophage antigen complex-1 (MAC-1) or glial fibrillary acidic protein (GFAP) immunocytochemistry, respectively. RT-PCR analysis shows the upregulation of inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α in microglia in the SN in vivo, indicating the activation of the inflammatory system. By contrast, treatment with capsaicin (a specific TRPV1 agonist) increased the survival of dopamine neurons in the SN and their fibers and dopamine levels in the STR in MPTP mice. Capsaicin neuroprotection is accompanied by inhibiting MPTP-induced glial activation and production of inflammatory cytokines. Treatment with AM251 and AM630 (CB1/2 antagonists) abolished capsaicin-induced beneficial effects, indicating the existence of a functional crosstalk between CB and TRPV1. Moreover, treatment with anandamide (an endogenous agonist for both CB and TRVP1) rescued nigrostriatal dopamine neurons and reduced gliosis-derived neuroinflammatory responses in MPTP mice. These results suggest that the cannabinoid and vanilloid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with neuroinflammation.

中文翻译：

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CB和TRPV1受体之间的功能性串扰可保护帕金森氏病MPTP模型中的尼古丁纹状体多巴胺能神经元

本研究检查了大麻素（CB）和1型瞬时电位受体香草类（TRPV1）之间的串扰是否有助于1-甲基-4-苯基-1,2,3,6-四氢吡啶中黑质纹状体多巴胺神经元的存活（ MPTP）帕金森氏病（PD）小鼠模型。如酪氨酸羟化酶（TH）或巨噬细胞抗原复合物1（MAC-1）或神经胶质纤维酸性蛋白（GFAP）所示，MPTP导致黑质黑质（SN）和纹状体（STR）的黑质纹状体多巴胺神经元大量丢失和神经胶质激活。 ）免疫细胞化学。RT-PCR分析显示诱导型一氧化氮合成酶的上调，白细胞介素1 β，和肿瘤坏死因子α在SN体内的小胶质细胞中，提示炎症系统已激活。相比之下，辣椒素（一种特殊的TRPV1激动剂）治疗可增加MPTP小鼠SN及其纤维中多巴胺神经元的存活率和STR中多巴胺水平。辣椒素的神经保护作用伴随着抑制MPTP诱导的神经胶质激活和炎性细胞因子的产生。AM251和AM630（CB1 / 2拮抗剂）治疗消除了辣椒素诱导的有益作用，表明CB和TRPV1之间存在功能性串扰。此外，用anandamide（CB和TRVP1的内源性激动剂）治疗可以挽救黑质纹状体多巴胺神经元，并减少MPTP小鼠神经胶质源性神经炎反应。