Weerasinghe-Mudiyanselage Poornima D E, Ang Mary Jasmin, Wada Mai, Kim Sung-Ho, Shin Taekyun, Yang Miyoung, Moon Changjong
Department of Veterinary Anatomy, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea.
Department of Basic Veterinary Sciences, College of Veterinary Medicine, University of the Philippines Los Baños, Los Baños 4031, Philippines.
Brain Sci. 2021 Jun 23;11(7):833. doi: 10.3390/brainsci11070833.
Among the animal models of Parkinson's disease (PD), the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model has shown both dopaminergic (DA) damage and related motor control defects, as observed in patients with PD. Recent studies have suggested that the DA system interacts with the synaptic plasticity of the hippocampus in PD. However, little is known about how alterations in the hippocampal structural plasticity are affected by the DA damage in MPTP-lesioned models. In the present study, we investigated alterations in dendritic complexity and spine density in the mouse hippocampus following acute MPTP treatment (22 mg/kg, intraperitoneally, four times/day, 2-h intervals). We confirmed that acute MPTP treatment significantly decreased initial motor function and persistently reduced the number of tyrosine hydroxylase-positive DA neurons in the substantia nigra. Golgi staining showed that acute MPTP treatment significantly reduced the spine density of neuronal dendrites in the cornu ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions of the mouse hippocampus at 8 and 16 days after treatment, although it did not affect dendritic complexity (e.g., number of crossing dendrites, total dendritic length, and branch points per neuron) in both CA1 and DG subregions at all time points after treatment. Therefore, the present study provides anatomical evidence that acute MPTP treatment affects synaptic structure in the hippocampus during the late phase after acute MPTP treatment in mice, independent of any changes in the dendritic arborization of hippocampal neurons. These findings offer data for the ability of the acute MPTP-lesioned mouse model to replicate the non-nigrostriatal lesions of clinical PD.
在帕金森病（PD）的动物模型中，1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）损伤的小鼠模型表现出多巴胺能（DA）损伤以及相关的运动控制缺陷，这与PD患者的情况一致。最近的研究表明，在PD中DA系统与海马体的突触可塑性相互作用。然而，在MPTP损伤模型中，海马体结构可塑性的改变如何受到DA损伤的影响却知之甚少。在本研究中，我们调查了急性MPTP处理（22mg/kg，腹腔注射，每天4次，间隔2小时）后小鼠海马体中树突复杂性和棘密度的变化。我们证实，急性MPTP处理显著降低了初始运动功能，并持续减少了黑质中酪氨酸羟化酶阳性DA神经元的数量。高尔基染色显示，急性MPTP处理在处理后8天和16天显著降低了小鼠海马体海马角1（CA1）顶/基部和齿状回（DG）亚区神经元树突的棘密度，尽管在处理后的所有时间点，它对CA1和DG亚区的树突复杂性（如交叉树突数量、总树突长度和每个神经元的分支点）均无影响。因此，本研究提供了解剖学证据，表明急性MPTP处理在小鼠急性MPTP处理后的后期会影响海马体中的突触结构，而与海马体神经元树突分支的任何变化无关。这些发现为急性MPTP损伤小鼠模型复制临床PD非黑质纹状体损伤的能力提供了数据。
