Subthalamic nucleus deep brain stimulation does not alter growth factor expression in a rat model of stable dopaminergic deficiency.

ABSTRACT

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been a highly effective treatment option for mid-to-late-stage Parkinson's disease (PD) for decades. Besides direct effects on brain networks, neuroprotective effects of STN-DBS - potentially via alterations of growth factor expression levels - have been proposed as additional mechanisms of action. OBJECTIVE: In the context of clarifying DBS mechanisms, we analyzed brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels in the basal ganglia, motor and parietal cortices, and dentate gyrus in an animal model of stable, severe dopaminergic deficiency. METHODS: We applied one week of continuous unilateral STN-DBS in a group of stable 6-hydroxydopamine (6-OHDA) hemiparkinsonian rats (6-OHDASTIM) in comparison to a 6-OHDA control group (6-OHDASHAM) as well as healthy controls (CTRLSTIM and CTRLSHAM). BDNF and GDNF levels were determined via ELISAs. RESULTS: The 6-OHDA lesion did not result in a persistent alteration in either BDNF or GDNF levels in a model of severe dopaminergic deficiency after completion of the dopaminergic degeneration. STN-DBS modestly increased BDNF levels in the entopeduncular nucleus, but even impaired BDNF and GDNF expression in cortical areas. CONCLUSIONS: STN-DBS does not increase growth factor expression when applied to a model of completed, severe dopaminergic deficiency in contrast to other studies in models of modest and ongoing dopaminergic degeneration. In healthy controls, STN-DBS does not influence BDNF or GDNF expression. We consider these findings relevant for clinical purposes since DBS in PD is usually applied late in the course of the disease.