Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases due to the loss of dopaminergic neurons in the midbrain in the substantia nigra. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic agent causing disruptions in mitochondria of dopaminergic neurons leading to impaired oxidant-antioxidant balance. Both zebrafish and zebrafish embryos are sensitive to MPTP. In zebrafish embryos, MPTP decreases the dopaminergic cells in the diencephalon by damaging dopaminergic neurons. Morphine is an opioid pain killer and a strong analgesic that is used to treat chronic pain. Until today morphine has been shown to regulate the survival or death of neurons and both protective and destructive effects of morphine have been reported in the central nervous system. This study aimed to evaluate the effects of morphine in MPTP-exposed zebrafish embryos. Developmental parameters were monitored and documented daily during embryonic development. Locomotor activity of zebrafish embryos at 96 h postfertilization (hpf) was determined. Acetylcholinesterase (AChE) activity and oxidant-antioxidant parameters were analyzed by biochemical methods. RT-PCR was used to evaluate bdnf, dj1, lrrk and pink1 expressions. Morphine treatment improved mortality and hatching rates, locomotor activity, AChE, and antioxidant enzyme activities as well as the expressions of bdnf, dj1, lrrk and pink1 in a dose-dependent manner that were altered by MPTP. Increased lipid peroxidation supports the role of morphine to induce autophagy to prevent PD-related pathologies. Our study provided important data on the possible molecular mechanism of the therapeutic effects of morphine in PD.

摘要

帕金森病 (PD) 是最常见的神经退行性疾病之一，原因是黑质中脑中的多巴胺能神经元丢失。1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 是一种神经毒剂，会破坏多巴胺能神经元的线粒体，从而导致氧化剂-抗氧化剂平衡受损。斑马鱼和斑马鱼胚胎都对 MPTP 敏感。在斑马鱼胚胎中，MPTP 通过破坏多巴胺能神经元来减少间脑中的多巴胺能细胞。吗啡是一种阿片类镇痛剂和强镇痛剂，用于治疗慢性疼痛。直到今天，吗啡已被证明可以调节神经元的存活或死亡，并且已经报道了吗啡在中枢神经系统中的保护和破坏作用。本研究旨在评估吗啡对暴露于 MPTP 的斑马鱼胚胎的影响。在胚胎发育期间每天监测和记录发育参数。确定了斑马鱼胚胎在受精后 96 小时 (hpf) 的运动活动。通过生化方法分析乙酰胆碱酯酶 (AChE) 活性和氧化剂-抗氧化剂参数。RT-PCR 用于评估bdnf、dj1、lrrk和pink1表达式。吗啡处理以剂量依赖的方式改善了死亡率和孵化率、运动活性、乙酰胆碱酯酶和抗氧化酶活性以及bdnf、dj1、lrrk和pink1的表达，而 MPTP 改变了这种方式。增加的脂质过氧化支持吗啡诱导自噬以预防 PD 相关病理的作用。我们的研究为吗啡治疗 PD 的可能分子机制提供了重要数据。