Department of Physiology, Akdeniz University, Medical School, Antalya, Turkey.
Department of Physiology, Akdeniz University, Medical School, Antalya, Turkey.
Brain Res. 2021 Jul 1;1762:147442. doi: 10.1016/j.brainres.2021.147442. Epub 2021 Mar 19.
This study aims to explore the effect of chronic central neuropeptide-S (NPS) treatment on gastrointestinal dysmotility and the changes of cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) of a Parkinson's disease (PD) rat model. The PD model was induced through a unilateral medial forebrain bundle (MFB) administration of the 6-hydroxydopamine (6-OHDA). Locomotor activity (LMA), solid gastric emptying (GE), and gastrointestinal transit (GIT) were measured 7 days after the surgery. NPS was daily administered (1 nmol, icv, 7 days). In substantia nigra (SN), dorsal motor nucleus of the vagus (DMV), and gastric whole-mount samples, changes in tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), glial fibrillary acidic protein (GFAP), NPS receptor (NPSR), and alpha-synuclein (Ser129) were examined by immunohistochemistry. Cuprolinic blue staining was used to evaluate the number of neuronal cells in myenteric ganglia. The GIT rate, the total number of myenteric neurons, and the expressions of ChAT, nNOS, TH, and GFAP in the myenteric plexus were not changed in rats that received the 6-OHDA. Chronic NPS treatment reversed 6-OHDA-induced impairment of the motor performance, and GE, while preventing the loss of dopaminergic and cholinergic neurons in SN and DMV, respectively. NPS attenuated 6-OHDA-induced α-syn (Ser129) pathology both in SN and DMV. Additionally, expression of NPSR protein was detected in gastro-projecting cells in DMV. Taken together, centrally applied NPS seems to prevent 6-OHDA-induced gastric dysmotility through a neuroprotective action on central vagal circuitry.
本研究旨在探讨慢性中枢神经肽 S（NPS）治疗对帕金森病（PD）大鼠模型胃肠道动力障碍的影响，以及背侧迷走神经运动核（DMV）胆碱能神经元的变化。通过单侧中脑束（MFB）给予 6-羟多巴胺（6-OHDA）诱导 PD 模型。手术后 7 天测量运动活性（LMA）、固体胃排空（GE）和胃肠道转运（GIT）。NPS 每天（1 nmol，icv，7 天）给药。在黑质（SN）、迷走神经运动核（DMV）和胃全层样本中，通过免疫组织化学检测酪氨酸羟化酶（TH）、胆碱乙酰转移酶（ChAT）、神经元型一氧化氮合酶（nNOS）、胶质纤维酸性蛋白（GFAP）、NPS 受体（NPSR）和α-突触核蛋白（Ser129）的变化。铜蓝蛋白染色用于评估肌间神经节神经元细胞的数量。接受 6-OHDA 治疗的大鼠，GIT 率、肌间神经元总数以及肌间神经丛中 ChAT、nNOS、TH 和 GFAP 的表达均无变化。慢性 NPS 治疗逆转了 6-OHDA 引起的运动功能障碍和 GE 损伤，同时分别防止了 SN 和 DMV 中多巴胺能和胆碱能神经元的丢失。NPS 减轻了 6-OHDA 诱导的 SN 和 DMV 中α-突触核蛋白（Ser129）病理。此外，NPSR 蛋白在 DMV 中的胃投射细胞中被检测到。总之，中枢应用 NPS 似乎通过对中枢迷走神经回路的神经保护作用来预防 6-OHDA 引起的胃动力障碍。
