Session Information
Date: Monday, June 20, 2016
Session Title: Surgical Therapy
Session Time: 12:30pm-2:00pm
Objective: To determine if subthalamic nucleus (STN)-deep brain stimulation (DBS) leads to a measurable functional improvement of motor deficits in an AAV1/2 A53T α-synuclein (aSyn) rat model of Parkinson’s disease (PD).
Background: DBS of the STN is one of the most effective therapies of motor symptoms in PD. The exact mechanisms underlying DBS are still unclear. To unveil these mechanisms as a first step we aimed to generate a working rodent system by implementing STN-DBS in an aSyn overexpression PD rat model driven by AAV1/2 that mimics pathological hallmarks of PD and produces functional impairment measured by paw use asymmetry.
Methods: 25 adult male Sprague Dawley were unilaterally injected in the substantia nigra (SN) contralateral to the dominant forepaw, that was assessed by the single pellet reaching task, either with 2 µl of AAV1/2 A53T aSyn (n=18) or AAV1/2 empty vector (EV; n=7) at a concentration of 2.55 x 10exp12 gp/ml. At day 21 all animals underwent microelectrode guided implantation of DBS electrodes into the STN on the same side. Cohorts of rats were divided into two interventional groups: activated stimulation (stim-ON; aSyn, n=9 and EV, n=4) and unactivated stimulation (stim-OFF; aSyn, n=9 and EV, n=3). In the interventional groups, stimulation was activated the same day using standard parameters and lasted for three weeks (day 42) whereas the control groups remained off stimulation. To assess baseline motor performance the single pellet reaching task was conducted before injection of AAV1/2, then again before DBS implantation (day 21) and at the end of the stimulation period (day 42) to assess the effect of stimulation.
Results: Functional impairment in the single pellet reaching task was observed in the A53T aSyn injected stim-OFF group 6 weeks after AAV1/2 injection compared to stim-OFF rats that received EV, establishing the effect of A53T aSyn. Functional deficits were partially restored in A53T aSyn stim-ON rats after three weeks of stimulation compared to the A53T aSyn stim-OFF rats, demonstrating the effect of DBS.
Conclusions: Motor deficits in forelimb use after AAV1/2 induced nigral overexpression of A53T aSyn in rats can be restored by STN-DBS and therefore our model can be used for further studies to elucidate the underlying mechanisms of DBS in Parkinson’s disease.
To cite this abstract in AMA style:
T. Musacchio, M. Rebenstorff, F. Fluri, C. Kleinschnitz, J.M. Brotchie, J. Volkmann, J.B. Koprich, C.W. Ip. Deep brain stimulation in the STN of a Parkinsonian rat model overexpressing human A53T α-synuclein in the substantia nigra – A proof of principle [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/deep-brain-stimulation-in-the-stn-of-a-parkinsonian-rat-model-overexpressing-human-a53t-synuclein-in-the-substantia-nigra-a-proof-of-principle/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-in-the-stn-of-a-parkinsonian-rat-model-overexpressing-human-a53t-synuclein-in-the-substantia-nigra-a-proof-of-principle/