帕金森氏症小鼠發病前腸道菌的長期研究

The longitudinal analysis of gut microbiota prior to the onset of motor dysfunctions in Parkinson's disease mouse model

梁風(Feng Liang)

指導教授 ： 陳示國

國立臺灣大學/生命科學院/生命科學系/碩士(2021年)

https://doi.org/10.6342/NTU202103215

摘要

帕金森氏症是最普遍的退化性神經疾病之一，其原因是α-突觸核蛋白不正常地堆積在神經細胞中(路易氏體)。帕金森氏症致病因素包括環境、基因背景甚至腸道菌的交互影響。研究顯示帕金森氏症患者的腸道菌會加重小鼠的運動功能障礙。然而在帕金森氏症中腸道菌是什麼時候以及如何發生變化是仍然未知。結合16S基因體定序分析以及運動行為測試，我們發現在過量表現變異人類α-突觸核蛋白帕金森氏症模型小鼠的腸道菌在成年時就已經發生腸道微生態失調，遠早於小鼠發病的年紀。另外，腸道菌的日夜週期性在帕金森氏症模型小鼠中也會漸漸地消失。由於紊亂的光週期如夜晚照光可以消弭腸道菌的週期性，在此研究中我們也證實當帕金森氏症模型小鼠暴露於夜晚低光的環境中運動行為會提早退化。這些研究顯示了生理時鐘-腸軸在帕金森氏症發病的影響，且可能提出一個影響病程的重要環境因素。

關鍵字

腸道菌 ； 生理時鐘 ； 帕金森氏症

並列摘要

Parkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders caused by the abnormal aggregation of alpha-synuclein (Lewy body) in neurons. The etiology of PD pathogenesis comes from a complex interplay between environmental and genetic factors. Previous studies have shown that circadian rhythms, gut microbiota are both associated with PD. However, when and how the dysbiosis in PD starts remains unclear. Combining 16S metagenomics analysis and locomotor activity tests, here we show that dysbiosis of the gut microbiome in the PD mice model with the SNCA p.A53T mutation can be detected as early as the time reaching adulthood. Besides, the diurnal oscillatory rhythms of gut microbiota are dampened by Parkinson’s disease progression. Furthermore, disruption of environmental light dark cycle such as dim light at night (dLAN) may accelerate motor impairment in the PD mice model. These findings reveal the impact of the circadian clock-gut microbiota axis on Parkinson's disease progression and may suggest a possible environmental factor in disease aggravation.

並列關鍵字

gut microbiota ； circadian rhythm ； Parkinson’s disease

參考文獻

Uncategorized References

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