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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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黑迷走神经通路控制胃动力并在帕金森病大鼠模型中受到影响

背景与目标

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枢，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。

方法

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末梢进行光遗传学刺激后，记录胃张力和胃动力。

结果

刺激 SNpc 通过激活背侧迷走神经复合体中的多巴胺 1 受体来增加胃张力和胃动力。在百草枯诱发的帕金森病模型中，这种黑质迷走神经通路在运动缺陷发展的早期阶段受到损害。

结论

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。