A Nigro-Vagal Pathway Controls Gastric Motility and Is Affected in a Rat Model of Parkinsonism.
A Nigro-Vagal Pathway Controls Gastric Motility and Is Affected in a Rat Model of Parkinsonism.
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DOI：
10.1053/j.gastro.2017.08.069
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发表时间：
2017-12
期刊：
影响因子：
29.4
通讯作者：
Travagli RA
中科院分区：
文献类型：
--
作者：
Anselmi L;Toti L;Bove C;Hampton J;Travagli RA
在大多数帕金森病患者中，胃肠道（GI）功能障碍，例如胃轻瘫和便秘，是该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神经毒剂后发生的，神经毒剂通过迷走神经影响脑-肠轴，然后传播到更高的中心，损害黑质致密部 (SNpc)，然后损害大脑皮层。我们的目的是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到损害。为了研究大鼠的这一神经通路，我们将示踪剂置于背侧迷走神经复合体（DVC）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，以诱导帕金森症或媒介物（对照）的特征。在 SNpc 中显微注射 NMDA 和/或 DVC 中黑迷走神经末梢的光遗传学刺激后记录胃张力和胃动力。刺激 SNpc 通过激活 DVC 中的多巴胺 1 受体来增加胃张力和胃动力。在百草枯诱导的帕金森病模型中，这种黑色迷走神经通路在运动缺陷发展的早期阶段受到损害。我们在大鼠中鉴定并表征了控制胃张力和运动的黑迷走神经单突触通路。该通路可能与早期帕金森病患者观察到的前驱期胃动力障碍有关。
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 following 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 (DVC) 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 following NMDA microinjection in the SNpc and/or optogenetic stimulation of nigro-vagal terminals in the DVC. Stimulation of the SNpc increased gastric tone and motility via activation of dopamine 1 receptors in the DVC. 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.
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