P 77 Pathological local field potential during the awake state in the progressive AAV-A53T-aSyn Parkinson's disease rat model

Abstract

Introduction: Abnormally enhanced beta (13–35 Hz) activity, recorded in the subthalamic nucleus (STN) of Parkinson’s disease (PD) patients and PD animal models, represents the electrophysiological biomarker of nigrostriatal degeneration. In this study, we investigated the local field potential (LFP) activity in the progressive AAV1/2-A53T-a-synuclein PD rat over an eight weeks period. Materials & Methods: To obtain LFP data from the motor cortex (MCx) and STN, Sprague Dawley rats were chronically implanted with monopolar electrodes using the coordinates 3 mm anterior from bregma, 3 mm right from medial line and 3.6 posterior from bregma, 2.5 mm right from medial line, 7.7 mm ventral from dura according to the Paxinos and Watson rat brain atlas and stereotaxically injected with AAV1/2 ipsilaterally in the substantia nigra (SN). To assess if neurodegeneration and putative pathological LFP development was dose-dependent, we injected three different concentrations of either 2 µl AAV1/2-A53T-aSyn or 2 µl empty vector (EV): 2.55 x 10 12 (low concentration), 5.1 x 10 12 (middle concentration), and 15.3 x 10 12 (high concentration) gp/ml. Following 2 weeks of recovery, LFP were recorded in awake animals during an alert rest state every two weeks over an eight weeks period. Beta power was calculated in the 13-30Hz frequency range and divided into two subgroups 13-20Hz (low beta) and 21-30Hz (high beta). After the last recording session, rats were sacrificed. The placement of STN electrodes was verified by Nissl staining and dopaminergic neuronal loss was identified by TH+ staining. Results: The high concentration AAV1/2-A53T-aSyn group of rats showed elevated total beta power due to high beta starting at the 2nd week in both MCx and STN (p < 0.05). All three AAV1/2-A53T-aSyn groups developed MCx high beta activity detected from week 4 until the end of the observation period (p < 0.05). Persistently elevated high beta power in the STN was observed from week 4 on in the middle concentration AAV1/2-A53T-aSyn group (p < 0.05). In addition, the low concentration AAV1/2-A53T-aSyn group showed elevated STN high beta activity at week 4 and 6 (p < 0.05). Conclusion: Our study indicates the progressive development of pathologically enhanced beta power in the A53T-aSyn Parkinson’s disease rat model in both MCx and STN. The onset of the pathological beta power is dose-dependent and disease-course-related.