Additional noradrenergic depletion aggravates forelimb akinesia and abnormal subthalamic nucleus activity in a rat model of Parkinson's disease

作者：Wang, Yong; Chen, Xiang; Wang, Tao; Sun, Yi Na; Han, Ling Na; Li, Bo Li; Zhang, Li; Wu, Zhong Heng; Huang, Chen; Liu, Jian^*

来源：Life Sciences, 2014, 119(1-2): 18-27.

DOI：10.1016/j.lfs.2014.10.007

• Parkinson's disease
• Akinesia
• Norepinephrine
• Subthalamic nucleus
• Firing pattem
• Oscillatory activity

Aims: This study aims to identify the contribution of additional noradrenergic depletion to forelimb akinesia and abnormal subthalamic nucleus (STN) firing activity in Parkinson's disease (PD). @@@ Main methods: Forelimb akinesia behaviors were tested in awake rats with noradrenergic N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions, unilateral 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra pars compacta (SNc) and with combined 6-OHDA and DSP-4 lesions. STN extracellular single-unit and local field potential (LIP) activities were examined in the animals that were anesthetized with urethane. @@@ Key findings: The adjusting steps and the contralateral touches of rats in the forelimb akinesia behavior tests were markedly inhibited by a further noradrenergic lesion with DSP-4 in 6-OHDA + DSP-4-lesioned group when compared with those of 6-OHDA-lesioned animals (P < 0.05 for all comparisons). Meanwhile, the neuronal firing pattern of STN also changed significantly towards more bursty in 6-OHDA + DSP-4-lesioned group (P < 0.05). Compared with 6-OHDA-lesioned animals, an additional noradrenergic lesion increased the 03-2.5 Hz oscillatory activity and the spike power of STN neurons (P < 0.01 for both comparisons), and strengthened the synchronized oscillation between subthalamic neuronal firing and LFP activity in 6-OHDA + DSP-4-lesioned group (P < 0.01). @@@ Significance: The results provide evidence to support the correlation between noradrenergic depletion and the further exaggerated dysfunction of STN electrical activity in PD and suggest that an aberrant noradrenergic system might play a specific role in the motor deficits of PD.

• 出版日期2014-12-5
• 单位西安交通大学