Abstract
Deep brain stimulation of the subthalamic nucleus (DBS-STN) is an effective treatment for advanced motor symptoms of Parkinson’s disease (PD). Recently, a connection between the limbic part of the STN and side effects of DBS-STN has been increasingly recognized. Animal studies have shown that DBS-STN influences behavior and provokes neurochemical changes in regions of the limbic system. Some of these regions, which are activated during DBS-STN, are involved in neuroimmunomodulation. The therapeutic effects of DBS-STN in PD treatment are clear, but the influence of DBS-STN on peripheral immunity has not been reported so far. In this study, we examined the effects of unilateral DBS-STN applied in male Wistar rats with 6-hydroxydopamine PD model (DBS-6OHDA) and rats without nigral dopamine depletion (DBS) on corticosterone (CORT) plasma concentration, blood natural killer cell cytotoxicity (NKCC), leukocyte numbers, lymphocyte population and apoptosis numbers, plasma interferon gamma (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) concentration. The same peripheral immune parameters we measured also in non-stimulated rats with PD model (6OHDA). We observed peripheral immunity changes related to PD model. The NKCC and percentage of T cytotoxic lymphocytes were enhanced, while the level of lymphocyte apoptosis was down regulated in 6OHDA and DBS-6OHDA groups. After DBS-STN (DBS-6OHDA and DBS groups), the plasma CORT and TNF-α were elevated, the number of NK cells and percentage of apoptosis were increased, while the number of B lymphocytes was decreased. We also found, changes in plasma IFN-γ and IL-6 levels in all the groups. These results suggest potential peripheral immunomodulative effects of DBS-STN in the rat model of PD. However, further studies are necessary to explain these findings and their clinical implication.Graphical Influence of deep brain stimulation of the subthalamic nucleus on peripheral immunity in rat model of Parkinson’s disease.
Highlights
Numerous structural and functional connectivity studies have indicated that the subthalamic nucleus (STN) is an important point of integration of both motor and associative/limbic inputs into the basal ganglia circuit (Haegelen et al 2009; Baunez et al 2011)
We demonstrated that limbic regions such as the medial septum (MS) (Podlacha et al 2016), bed nucleus of the stria terminalis (BST) (Myślińska et al 2012) and ventral tegmental area (VTA) (Wrona et al 2004) are involved in neuroimmunomodulation in rats
Spectacular effects of Deep brain stimulation of the subthalamic nucleus (DBS-STN) in Parkinson’s disease (PD) patients may occur with neuropsychiatric complications (Nassery et al 2016)
Summary
Numerous structural and functional connectivity studies have indicated that the subthalamic nucleus (STN) is an important point of integration of both motor and associative/limbic inputs into the basal ganglia circuit (Haegelen et al 2009; Baunez et al 2011). This observation confirms motor and non-motor effects of deep brain subthalamic nucleus stimulation (DBS-STN) used for the treatment of Parkinson’s disease (PD) patients (Nassery et al 2016), and seen in animal model data (Baunez et al 2011). Some of the limbic regions activated during DBS-STN in rats are involved in neuroimmunomodulation (Wrona 2006)
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