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Gut dysbiosis aggravates cognitive deficits,amyloid pathology and lipid metabolism dysregulation in a transgenic mouse model of Alzheimer's disease

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Journal of Pharmaceutical Analysis 2023年第12期13卷 1526-1547页

作者： Chang Qu Qing-Qing Xu Wen Yang Mei Zhong Qiuju Yuan Yan-Fang Xian Zhi-Xiu Lin School of Chinese Medicine Faculty of MedicineThe Chinese University of Hong KongHong KongChina College of Forestry and Landscape Architecture South China Agricultural UniversityGuangzhou510640China Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong Science ParkShatinN.T.Hong KongChina Hong Kong Institute of Integrative Medicine The Chinese University of Hong KongHong KongChina

Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic *** N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD *** this study,the cognitive function and gut microbiota of tgcrnd8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,*** pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of *** choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive *** results showed that gut dysbiosis,neuroinflammation response,Ab deposition,tau hyperphosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice *** microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the *** the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuroinflammation,Ab deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg ***,excessive choline treatment was also shown to aggravate the cognitive deficits,Ab deposition,neuroinflammation and CDK5/STAT3 pathway *** findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.

关键词： Alzheimer's disease Gut dysbiosis Neuropathology tgcrnd8 mice

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