Polymannuronic acid prevented dopaminergic neuronal loss via brain-gut-microbiota axis in Parkinson’s disease model

PD model mice were pretreated with PM via oral gavage one time per day for 4 weeks and the preventative effects of Polymannuronic acid (PM) against neuronal loss together with its modulation on the brain-gut-microbiota axis were systematically explored. PM administration improved motor functions by preventing dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) and enhanced contents of several neurotransmitters in the striatum of PD mice. Mechanism results showed PM reshaped gut microbiota in a positive way against PD neurodegeneration and increased the production of fecal SCFAs in the colon of PD mice. PM treatment-induced transcripts benefiting neuroprotection but suppressed transcripts aggravating neurodegeneration in the colon of PD mice. In particular, PM alleviated intestinal and systematic inflammation in PD.

本研究采用每日一次灌胃给药的方式，以聚甘露糖醛酸（Polymannuronic acid, PM）对帕金森病（Parkinson's disease, PD）模型小鼠开展为期4周的预处理，并系统探究了PM对抗神经元丢失的预防作用，及其对脑-肠-微生物轴的调控效应。结果表明，PM给药可通过阻止黑质致密部（substantia nigra pars compacta, SNpc）内多巴胺能神经元的丢失，改善PD模型小鼠的运动功能，并提升其纹状体中多种神经递质的含量。机制研究结果显示，PM可正向重塑肠道菌群以对抗PD相关神经退行性病变，同时增加PD模型小鼠结肠内粪便短链脂肪酸（short-chain fatty acids, SCFAs）的生成。PM处理可上调PD模型小鼠结肠中有益于神经保护的转录本，并抑制加剧神经退行性病变的转录本表达。尤为值得注意的是，PM可缓解PD模型小鼠的肠道炎症与全身性炎症。