Subthalamic nucleus deep brain stimulation induces nigrostriatal dopaminergic plasticity in a stable rat model of Parkinson’s disease

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Abstract
Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been a highly effective treatment option for middle to late stage Parkinson’s disease for decades. Though, the underlying mechanisms of action, particularly effects on the cellular level, remain in part unclear. In the context of identifying disease-modifying effects of STN-DBS by prompting cellular plasticity in midbrain dopaminergic systems, we analyzed neuronal tyrosine hydroxylase and c-Fos expression in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Methods: We applied 1 week of continuous unilateral STN-DBS in a group of stable 6-hydroxydopamine (6-OHDA) hemiparkinsonian rats (STNSTIM) in comparison to a 6-OHDA control group (STNSHAM). Immunohistochemistry identified NeuN+, tyrosine hydroxylase+ and c-Fos+ cells within the SNpc and VTA. Results: After 1 week, rats in the STNSTIM group had 3.5-fold more tyrosine hydroxylase+ neurons within the SNpc (P = 0.010) but not in the VTA compared to sham controls. There was no difference in basal cell activity as indicated by c-Fos expression in both midbrain dopaminergic systems. Conclusion: Our data support a neurorestorative effect of STN-DBS in the nigrostriatal dopaminergic system already after 7 days of continuous STN-DBS in the stable Parkinson’s disease rat model without affecting basal cell activity.

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