Grembecka Beata, Glac Wojciech, Listowska Magdalena, Jerzemowska Grażyna, Plucińska Karolina, Majkutewicz Irena, Badtke Piotr, Wrona Danuta
Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, 59 Wita Stwosza Str, 80-308, Gdańsk, Poland.
Department of Physiology, Medical University of Gdańsk, 1 Dębinki Str, 80-211, Gdańsk, Poland.
J Neuroimmune Pharmacol. 2021 Jun;16(2):454-469. doi: 10.1007/s11481-020-09934-7. Epub 2020 Jul 9.
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 Abstract Influence of deep brain stimulation of the subthalamic nucleus on peripheral immunity in rat model of Parkinson's disease.
丘脑底核深部脑刺激术（DBS-STN）是治疗帕金森病（PD）晚期运动症状的一种有效方法。最近，人们越来越认识到丘脑底核的边缘部分与DBS-STN的副作用之间存在联系。动物研究表明，DBS-STN会影响行为，并引发边缘系统区域的神经化学变化。其中一些在DBS-STN过程中被激活的区域参与神经免疫调节。DBS-STN在PD治疗中的疗效是明确的，但迄今为止，DBS-STN对外周免疫的影响尚未见报道。在本研究中，我们检测了对雄性Wistar大鼠应用单侧DBS-STN，其中包括6-羟基多巴胺帕金森病模型大鼠（DBS-6OHDA）和未发生黑质多巴胺耗竭的大鼠（DBS），观察其对皮质酮（CORT）血浆浓度、血液自然杀伤细胞细胞毒性（NKCC）、白细胞数量、淋巴细胞亚群及凋亡数量、血浆干扰素γ（IFN-γ）、白细胞介素6（IL-6）和肿瘤坏死因子（TNF-α）浓度的影响。我们还对未接受刺激的帕金森病模型大鼠（6OHDA）测量了相同的外周免疫参数。我们观察到与帕金森病模型相关的外周免疫变化。在6OHDA和DBS-6OHDA组中，NKCC及细胞毒性T淋巴细胞百分比升高，而淋巴细胞凋亡水平下调。在进行DBS-STN后（DBS-6OHDA和DBS组），血浆CORT和TNF-α升高，NK细胞数量及凋亡百分比增加，而B淋巴细胞数量减少。我们还发现，所有组的血浆IFN-γ和IL-6水平均有变化。这些结果表明，DBS-STN在帕金森病大鼠模型中具有潜在的外周免疫调节作用。然而，需要进一步研究来解释这些发现及其临床意义。图形摘要：丘脑底核深部脑刺激对帕金森病大鼠模型外周免疫的影响
