Parkinson's disease (PD) is a debilitating condition resulting in motor and non-motor symptoms affecting approximately 10 million people worldwide. Currently, there are no pharmacological treatments that can cure the condition or effectively halt its progression. The focus of PD research has been primarily on the neurobiological basis and consequences of dopamine (DA) neuron degeneration given that the loss of DA neurons projecting from the substantia nigra to the dorsal striatum results in the development of cardinal PD motor symptoms. Alternatively, gastrointestinal dysfunction is well recognized in PD patients, and often occurs prior to the development of motor symptoms. The gut microbiota, which contains thousands of bacterial species, play important roles in intestinal barrier integrity and function, metabolism, immunity and brain function. Pre-clinical and clinical studies suggest an important link between alterations in the composition of the gut microbiota and psychiatric and neurological conditions, including PD. Several reports have documented gut dysbiosis and alterations in the composition of the gut microbiota in PD patients. Therefore, the goal of this study was to explore the contribution of the gut microbiota to the behavioral and neurochemical alterations in a rodent toxin model of DA depletion that reproduces the motor symptoms associated with PD. We observed that chronic treatment of adult rats with non-absorbable antibiotics ameliorates the neurotoxicity of 6-hydroxydopamine (6-OHDA) in a unilateral lesion model. Specifically, immunohistochemistry against the dopaminergic neuron marker tyrosine hydroxylase (TH) showed an attenuation of the degree of 6-OHDA-induced dopaminergic neuron loss in antibiotic treated animals compared to control animals. In addition, we observed a reduction in the expression of pro-inflammatory markers in the striatum of antibiotic-treated animals. The degree of motor dysfunction after 6-OHDA was also attenuated in antibiotic-treated animals as measured by paw-rearing measurements in the cylinder test, forepaw stepping test, and ipsilateral rotations observed in the amphetamine-induced rotation test. These results implicate the gut microbiota as a potential contributor to pathology in the development of PD. Further studies are necessary to understand the specific mechanisms involved in transducing alterations in the gut microbiota to changes in dopaminergic neuron loss and motor dysfunction.

中文翻译：

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在帕金森氏病的啮齿动物模型中，用抗生素改变肠道菌群可保护多巴胺神经元丢失并改善运动功能障碍。

帕金森氏病（PD）是一种使人衰弱的疾病，会导致运动和非运动症状，影响全世界约1000万人。当前，没有药物疗法可以治愈该病症或有效地阻止其进展。PD研究的重点主要集中在神经生物学基础和多巴胺（DA）神经元变性的后果上，因为从黑质投射到背侧纹状体的DA神经元的丧失会导致主要的PD运动症状的发展。备选地，胃肠功能障碍在PD患者中是公认的，并且通常在运动症状发展之前发生。包含数千种细菌的肠道菌群在肠道屏障的完整性和功能，新陈代谢，免疫力和脑功能。临床前和临床研究表明，肠道菌群组成的变化与包括PD在内的精神病和神经病之间存在重要的联系。几篇报道记录了PD患者的肠道营养不良和肠道菌群组成的改变。因此，本研究的目的是探讨DA耗竭的啮齿动物毒素模型中肠道菌群对行为和神经化学变化的贡献，该模型再现了与PD相关的运动症状。我们观察到，用不可吸收的抗生素对成年大鼠进行慢性治疗可改善单侧病变模型中6-羟基多巴胺（6-OHDA）的神经毒性。具体来说，与对照动物相比，针对多巴胺能神经元标志物酪氨酸羟化酶（TH）的免疫组织化学研究显示，在抗生素治疗的动物中，6-OHDA诱导的多巴胺能神经元损失的程度有所减轻。此外，我们观察到抗生素治疗动物的纹状体中促炎性标志物表达的减少。通过在气瓶试验，前爪踩踏试验和苯丙胺诱导的旋转试验中观察到的同侧旋转测量的抗生素治疗动物中，6-OHDA后的运动功能障碍程度也有所减轻。这些结果暗示了肠道菌群可能是PD发展中病理学的潜在因素。