Objective: To investigate the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on striatal dopamine transporter (DAT) of Parkinsonian rat models.

Background: STN-DBS has become an effective treatment option in advanced Parkinson’s disease (PD). Whether STN-DBS would affect the striatal dopamine levels remains unclear.

Methods: Fourty healthy male Sprague-Dawley rats were randomly divided into four groups: PD rat model group, normal rat group, PD rat model treated with DBS group and normal rat treated with DBS group. PD rat model received unilaterally administered 6-OHDA in the right MFB with two points. Deep brain stimulation electrode was stereotactic implanted in STN at right side. The rats treate with DBS received stimulation for two weeks (frequency 130Hz, pulse width 60us, voltage 1.0V, 30 minutes/day). Apomorphine rotation test and Cylinder test were used to assess the behavioral changes in rats. [11C]CFT PET was performed to assess the changes of dopamine transporter in rats. Tyrosine hydroxylase (TH) immunohistochernical staining was used to detect the change of dopaminergic neurons in all groups of rats.

Results: After two weeks of STN stimulation, there was a significant reduction of apomorphine-induced rotation in PD rat models. Cylinder trials suggest that the number of forelimb activity significantly increased from 0.4 ± 0.3 beats / min at pre-stimulation state to 0.8 ± 0.5 beats/min after stimulation, and the ratio of limb-use asymmetry significantly decreased from 91.3 ± 9.5% at pre-stimulation state to 75.1 ± 8.6% after stimulation. [11C]CFT PET imaging showed significantly decreased DAT binding in the lesion side (right side) of striatum of PD rat models while DAT binding was symmetry in bilateral striatum of normal rats. After two weeks of STN stimulation, there was a significant increase of DAT binding in the right side striatum in both normal rats and PD rat models. Average asymmetry index (AI) changed from -5.58 ± 2.66 at pre-stimulation state to -9.42 ± 3.91 after stimulation in normal rats. Average AI decreased from 28.54 ± 8.66 at pre-stimulation state to 19.10 ± 6.60 after stimulation in PD rat models. There was no significant change of TH immunohistochemistry after STN stimulation in both normal rats and PD rat models.

Conclusions: STN-DBS could improve the behavior function of PD rat models. STN-DBS could increase striatal DAT in both normal rats and PD rat models, suggesting it could influence the release or metabolism of striatal dopamine.

References: 1.Sossi V, Dinelle K, Topping GJ, et al. Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat model of Parkinson’s: an in vivo imaging study.J Neurochem 2009;109:85-92. 2. Pazo JH, Höcht C, Barceló AC, et al. Effect of electrical and chemical stimulation of the subthalamic nucleus on the release of striatal dopamine.Synapse 2010;64:905-915.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-subthalamic-nucleus-stimulation-on-striatal-dopamine-transporter-in-parkinsonian-rat-models/