Acute MPTP Treatment Impairs Dendritic Spine Density in the Mouse Hippocampus.

Poornima D E Weerasinghe-Mudiyanselage,Mary Jasmin Ang,Taekyun Shin,Miyoung Yang,Sung-Ho Kim,Changjong Moon,Mai Wada

doi:10.3390/brainsci11070833

Abstract

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.

Highlights

IntroductionSeveral animal models have been used to explore the pathogenic pathways of Parkinson’s disease (PD), as well as the therapeutic mechanisms against it, because no single model is likely to be appropriate in all studies [2]
To confirm that MPTP lesioning had occurred in the brains, immunohistochemistry for tyrosine hydroxylase (TH) expression in the substantia nigra was performed at different time points (1, 8, and 16 days)
We confirmed that acute MPTP treatment led to impaired dendritic spine density in the cornu ammonis 1 (CA1) and dentate gyrus (DG) subregions of the hippocampus in the late phase without any alterations in the dendritic complexity, suggesting that the changes of the dendritic spines in the hippocampus might be related to the non-motor, Parkinson’s disease (PD)-like symptoms

Summary

Introduction

Several animal models have been used to explore the pathogenic pathways of PD, as well as the therapeutic mechanisms against it, because no single model is likely to be appropriate in all studies [2]. As major vulnerable brain regions in the DA system, the substantia nigra and striatum have been a focus of research into pathological changes in PD. In both patients with PD and MPTP-lesioned models, striatal DA denervation appears to be related to the reduced dendritic length and spine number in this brain region [3,4,5,6]. MPTP administration altered synaptic plasticity in the hippocampus, suggesting that the DA system interacts with neuronal plasticity in the hippocampus [7,8]

Methods

Results

Discussion

Conclusion