A time-course study of behavioral and electrophysiological characteristics in a mouse model of different stages of Parkinson's disease using 6-hydroxydopamine

Abstract

Parkinson's disease (PD) is characterized by abnormal motor symptoms and increased neuronal activity in the subthalamic nucleus (STN) as the disease progresses. We investigated the behavioral and electrophysiological characteristics in a mouse model mimicking the progressive stages of human PD (early, moderate, and advanced) by injecting 6-hydroxydopamine (6-0HDA) into the right medial forebrain bundle (MFB) at three different concentrations (2, 4, and 6 mu g/2 mu l). Significant changes in motor symptoms were demonstrated between groups in association with relative TH-positive cell loss in the substantia nigra pars compacta (SNc). Moreover, electrophysiologically assessed changes in the mean neuronal firing rate in the STN neurons were comparable to those in the early to advanced stages of human PD. Thus, the mouse model presented herein replicates the unique characteristics of each progressive stage of PD, in both motor and neurophysiological aspects, and therefore can be useful for further investigations of PD pathology. (C) 2015 Elsevier B.V. All rights reserved.