Guo Yinli, Liu Chengbo
Institute of Innovation and Entrepreneurship, Guizhou Education University, Guizhou, Wudang District, Guiyang City, China.
Medical section, Jiang Ling County People's Hospital, Hubei, Jiangling County, Jingzhou City, China.
PeerJ. 2025 Jan 21;13:e18788. doi: 10.7717/peerj.18788. eCollection 2025.
This study investigates the protective properties of melatonin in an Parkinson's disease (PD) model, focusing on the underlying mechanisms involving heat shock proteins (HSPs).
Twelve adult male C57BL/6 mice were randomly divided into four groups (normal control, melatonin control, Parkinson's model, and melatonin treatment; = 3 per group) and housed in a single cage. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected intraperitoneally in the Parkinson's model and treatment groups to establish a subacute PD model, while controls received saline. Limb motor ability was assessed 1 h after the final injection using behavioral tests, including the open field test to evaluate central zone entries and average movement. Dopamine transporter (DAT) expression in the striatum was analyzed by immunohistochemistry, and Western blot was used to measure autophagy proteins and HSP70 levels.
The PD mouse model was successfully established through MPTP stimulation. Compared to the normal control group, the model group showed a significant reduction in the frequency of entering the central zone and average movement. The number of DAT-positive cells in the brain also decreased significantly. The expression levels of HSP70 and CDK5 were significantly lower, while the expression levels of LC3 II /LC3I and p62 increased significantly. In the MT treatment group, both the frequency of entering the central zone and the average movement were significantly higher compared to the model group. DAT-positive cells in the midbrain also increased significantly. The expression levels of HSP70 and CDK5 were significantly elevated, while the expression levels of LC3 II /LC3I and p62 protein were significantly decreased.
Melatonin exerts a protective effect against MPP-induced damage to dopaminergic neurons, presumably by upregulating HSP70, which inhibits neuronal autophagy.
本研究调查褪黑素在帕金森病（PD）模型中的保护特性，重点关注涉及热休克蛋白（HSPs）的潜在机制。
将12只成年雄性C57BL/6小鼠随机分为四组（正常对照组、褪黑素对照组、帕金森病模型组和褪黑素治疗组；每组n = 3），单笼饲养。帕金森病模型组和治疗组腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）以建立亚急性PD模型，而对照组注射生理盐水。在最后一次注射后1小时，使用行为测试评估肢体运动能力，包括旷场试验以评估进入中央区域的次数和平均移动距离。通过免疫组织化学分析纹状体中多巴胺转运体（DAT）的表达，并使用蛋白质免疫印迹法测量自噬蛋白和HSP70水平。
通过MPTP刺激成功建立了PD小鼠模型。与正常对照组相比，模型组进入中央区域的频率和平均移动距离显著降低。脑中DAT阳性细胞数量也显著减少。HSP70和CDK5的表达水平显著降低，而LC3 II /LC3I和p62的表达水平显著升高。在褪黑素治疗组中，进入中央区域的频率和平均移动距离均显著高于模型组。中脑DAT阳性细胞也显著增加。HSP70和CDK5的表达水平显著升高，而LC3 II /LC3I和p62蛋白的表达水平显著降低。
褪黑素对MPP诱导的多巴胺能神经元损伤具有保护作用，可能是通过上调HSP70来抑制神经元自噬。
