Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To determine the therapeutic effects of Deep Brain Stimulation (DBS) in mice with Spinocerebellar Ataxia (SCA1).
Background: Ataxia is a movement disorder affecting balance and coordination of limbs, gait, eyes and speech. Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominantly inherited neurodegenerative disorder caused by the expansion of a CAG tract in exon 8 of the ATAXIN 1 gene affecting the brainstem, spinocerebellar tracts, and particularly Purkinje cells of the cerebellar cortex. Typically, symptoms worsen over time and result in death from complications related brainstem dysfunction. Currently, there is no effective cure or treatment for SCA1. An absence of the inhibitory signals to the deep cerebellar nuclei (DCN) results in hyperexcitability and thereby motor impairment. Hence, regulating the firing frequency of the DCN neurons could ameliorate symptoms of the disease. Hence we hypothesize that DBS can be used to alleviate ataxia in SCA1 mice.
Methods: 10-12 month old B05 mice were stereotactically implanted in the DCN with stainless steel, single channel, DBS electrodes (Plastics One). Mice in the “STIM” group underwent acute High Frequency Stimulation (HFS) for one week post recovery and mice in the “SHAM” group did not undergo any HFS. Mice were tested for gait ataxia using DigiGait® before DBS implantation, and again after DBS implantation and HFS. At the end of the experimental paradigm, mice were sacrificed and brains sectioned to confirm accuracy of electrode implantation.
Results: We were able to successfully implant DBS electrodes in DCN of B05 mice and treat them with acute HFS. B05 mice show several stride anomalies when compared to wildtype littermates. DigiGait assessment demonstrated marginal improvement in ataxic mice treated with HFS DBS, with respect to movement control and coordination. Hind paw area and the power generation of the hind paw during propulsion MAX dA/dT were returned to more wildtype values in HFS mice. This implies that our treatment at least corrects B05 mice for their lack of control and deceleration.
Conclusions: In this pilot study, we were able to target the deep cerebellar nuclei in B05 ataxic mice with DBS electrodes and perform acute HFS in these animals. Further, we were able to demonstrate marginal improvement in stride in the stimulated animals. Further work will be necessary to confirm our initial observations and obtain more success.
To cite this abstract in AMA style:V. Vedam-Mai, K. McFarland, Q. Zhang, H. Kim, R. Nathu, S. Kurtovic, K. Savery, T. Ashizawa, M.S. Okun. Evaluating the effects of deep brain stimulation (DBS) in mice with spinocerebellar ataxia (SCA1) [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/evaluating-the-effects-of-deep-brain-stimulation-dbs-in-mice-with-spinocerebellar-ataxia-sca1/. Accessed September 25, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluating-the-effects-of-deep-brain-stimulation-dbs-in-mice-with-spinocerebellar-ataxia-sca1/