Colonic Dopaminergic Neurons Changed Reversely With Those in the Midbrain via Gut Microbiota-Mediated Autophagy in a Chronic Parkinson's Disease Mice Model

• Published in: Frontiers in aging neuroscience 2021-04, Vol.13, p.649627
• Main Authors: Liu, Xin, Du, Zhong-Rui, Wang, Xiong, Luk, Kar-Him, Chan, Cheuk-Hin, Cao, Xu, Zhao, Qing, Zhao, Fang, Wong, Wing-Tak, Wong, Ka-Hing, Dong, Xiao-Li
• Format: Article
• Language: English
• Subjects: Abundance; Acetic acid; Animal models; Apoptosis; Autophagy; Behavior; Colon; Digestive system; dopamine; Dopamine receptors; Dysbacteriosis; Experiments; Fatty acids; Gastrointestinal diseases; Gastrointestinal tract; Hydroxylase; Injection; Intestinal microflora; Laboratories; Mesencephalon; Microbiota; Movement disorders; MPTP; Neostriatum; Nervous system; Neurodegenerative diseases; Neurons; Neuroscience; Parkinson's disease; Pathogenesis; Pathology; Phagocytosis; Propionic acid; short chain fatty acids; Small intestine; Substantia nigra; tyrosine hydroxylase
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2021.649627

The role of gut-brain axis in the pathogenesis of Parkinson's disease (PD) have become a research hotspot, appropriate animal model to study gut-brain axis in PD is yet to be confirmed. Our study employed a classical PD mice model achieved by chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) injection to study concurrent changes of dopaminergic neurons in the midbrain and the colon of mice. Our results showed such a PD model exhibited apparent locomotor deficits but not gastrointestinal dysfunction. Tyrosine hydroxylase expressions and dopamine content reduced greatly in the substantia nigra pars compacta (SNpc) or striatum, but increased in the colon of PD mice. Mechanism investigation indicated autophagy activity and apoptosis were stimulated in the SNpc, but inhibited in the colon of PD mice. Interplay of gut microbiota (GM) and autophagy in response to chronic MPTP injection led to GM dysbiosis and defective autophagy in mice colon. Meanwhile, fecal short chain fatty acids (SCFAs), acetate and propionate in particular, declined greatly in PD mice, which could be attributed to the decreased bacteria abundance of phylum , but increased abundance of phylum . GM dysbiosis derived fecal SCFAs might be one of the mediators of downregulated autophagy in the colon of PD mice. In conclusion, colonic dopaminergic neurons changed in the opposition direction with those in the midbrain via GM dysbiosis-mediated autophagy inhibition followed by suppressed apoptosis in response to chronic MPTP injection. Such a chronic PD mice model might not be an ideal model to study role of gut-brain axis in PD progression.