Anselmi Laura, Toti Luca, Bove Cecilia, Hampton Jessica, Travagli R Alberto
Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania.
Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania.
Gastroenterology. 2017 Dec;153(6):1581-1593. doi: 10.1053/j.gastro.2017.08.069. Epub 2017 Sep 11.
BACKGROUND & AIMS: In most patients with Parkinson's disease, gastrointestinal (GI) dysfunctions, such as gastroparesis and constipation, are prodromal to the cardinal motor symptoms of the disease. Sporadic Parkinson's disease has been proposed to develop after ingestion of neurotoxicants that affect the brain-gut axis via the vagus nerve, and then travel to higher centers, compromising the substantia nigra pars compacta (SNpc) and, later, the cerebral cortex. We aimed to identify the pathway that connects the brainstem vagal nuclei and the SNpc, and to determine whether this pathway is compromised in a rat model of Parkinsonism.
To study this neural pathway in rats, we placed tracers in the dorsal vagal complex or SNpc; brainstem and midbrain were examined for tracer distribution and neuronal neurochemical phenotype. Rats were given injections of paraquat once weekly for 3 weeks to induce features of Parkinsonism, or vehicle (control). Gastric tone and motility were recorded after N-methyl-d-aspartate microinjection in the SNpc and/or optogenetic stimulation of nigro-vagal terminals in the dorsal vagal complex.
Stimulation of the SNpc increased gastric tone and motility via activation of dopamine 1 receptors in the dorsal vagal complex. In the paraquat-induced model of Parkinsonism, this nigro-vagal pathway was compromised during the early stages of motor deficit development.
We identified and characterized a nigro-vagal monosynaptic pathway in rats that controls gastric tone and motility. This pathway might be involved in the prodromal gastric dysmotility observed in patients with early-stage Parkinson's disease.
在大多数帕金森病患者中，胃肠道功能障碍，如胃轻瘫和便秘，是该疾病主要运动症状的前驱症状。有人提出，散发性帕金森病是在摄入通过迷走神经影响脑-肠轴的神经毒物后发展而来的，这些毒物随后进入更高的中枢，损害黑质致密部（SNpc），随后损害大脑皮层。我们旨在确定连接脑干迷走神经核和SNpc的通路，并确定该通路在帕金森病大鼠模型中是否受损。
为了研究大鼠的这种神经通路，我们将示踪剂置于背侧迷走神经复合体或SNpc中；检查脑干和中脑的示踪剂分布和神经元神经化学表型。大鼠每周注射一次百草枯，持续3周以诱导帕金森病特征，或注射赋形剂（对照）。在SNpc中微量注射N-甲基-D-天冬氨酸和/或对背侧迷走神经复合体中的黑质-迷走神经终末进行光遗传学刺激后，记录胃张力和运动。
刺激SNpc通过激活背侧迷走神经复合体中的多巴胺1受体增加胃张力和运动。在百草枯诱导的帕金森病模型中，这种黑质-迷走神经通路在运动缺陷发展的早期阶段受损。
我们在大鼠中鉴定并表征了一条控制胃张力和运动的黑质-迷走神经单突触通路。该通路可能与早期帕金森病患者中观察到的前驱性胃动力障碍有关。
