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

Liu, Xin; Du, Zhong Rui; Wang, Xiong; Luk, Kar Him; Chan, Colin; Xu, Chang; Zhao, Qing; Zhao, Fang; Wong, Wing Tak; Wong, Ka Hing; Dong, Xiaoli

doi:10.3389/fnagi.2021.649627

Cited by 14 publications

(15 citation statements)

References 38 publications

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“…From the midbrain or striatum tissues, total proteins were extracted after being homogenized on ice in an ice-cold lysis buffer. Western-blot experiment methodology employed was the same as in our previously published studies [ 21 , 24 ]. Briefly, an equal number of proteins was separated using SDS-PAGE gels and transferred to PVDF membranes.…”

Section: Methodsmentioning

confidence: 99%

Selenium Forms and Dosages Determined Their Biological Actions in Mouse Models of Parkinson’s Disease

Sun

Liu

et al. 2022

Nutrients

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Selenium (Se), an essential antioxidant trace element, is reported to play a role in Parkinson’s disease (PD). However, there is a lack of systematic studies on different Se forms against PD. Our study is designed to compare the neuroprotective effects of inorganic and organic Se in two classical PD mice models and investigate the underlying mechanisms for their potentially differential actions against PD. In this study, different dosages of inorganic sodium selenite (Se-Na) or organic seleno-L-methionine (Se-Met) were fed to either acute or chronic PD mice models, and their neuroprotective effects and mechanisms were explored and compared. Se-Na provided better neuroprotective effects in PD mice than Se-Met administered at the same but at a relatively low Se dosage. Se-Na treatment could influence GPX activities but not their mRNA expressions in the midbrains of PD mice. The enhanced GPX activities caused by Se-Na, but not Se-Met, in PD mice could be the major reason for the positive actions of inorganic Se to prevent dopaminergic neuronal loss in this study. In vivo bio-distribution experiments found MPTP injection greatly changed Se bio-distribution in mice, which led to reversed alterations in the bioavailability of Se-Met and Se-Na. Se-Na had higher bioavailability than Se-Met in PD mice, which could explain its better neuroprotective effects compared to Se-Met. Our results proved that Se forms and dosages determined their biological actions in mouse models of PD. Our study will provide valuable scientific evidence to researchers and/or medical professionals in using Se for PD prevention or therapy.

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Section: Methodsmentioning

confidence: 99%

Selenium Forms and Dosages Determined Their Biological Actions in Mouse Models of Parkinson’s Disease

Sun

Liu

et al. 2022

Nutrients

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“…The gut microbiota changes found in colitis and rotenonetreated post-colitis mice in our study are similar to what has been observed in a study on another toxin-based PD mouse model, demonstrating an increasing trend in the RAs of Bacteroidetes and a decreased trend in the RAs of Firmicutes in PD mice [64][65][66] . In contrast, other studies show the opposite results 67 . We showed a lower abundance of Lactobacillus at the genus level in DSS alone and DSS+Rot group compared to the control group.…”

Section: Discussionmentioning

confidence: 87%

Intragastric administration of low-dose rotenone post-colitis exacerbates damage to the nigrostriatal dopaminergic system in Parkinson’s disease: The pace accelerates even more

Sharma

Thakkar

et al. 2022

Preprint

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Background: The contribution of gastrointestinal (GI) inflammation and local exposure to neurotoxins in the gut offers the most in-depth explanation of Parkinson's disease (PD) etiopathogenesis through abnormal accumulation and spreading of alpha-synuclein (α-syn) aggregates from the gut to the brain. Objectives: This study was designed to investigate whether dextran sodium sulfate (DSS)-mediated colitis may have lasting effects on dopaminergic pathways in the brain and whether or not colitis exacerbated susceptibility to later exposure to the neurotoxin rotenone. Methods: To induce chronic colitis, 10 months old C57BL/6 mice were pre-exposed to 3 cycles of 7 days of 1% (w/v) DSS administration in drinking water followed by 14 days of regular drinking water. After colitis-induction, animals received a low dose of intragastric rotenone for the next 8 weeks, followed by testing for Parkinsonian behavior and GI phenotypes of inflammation. At the end of the 8th week after colitis, colon, brain stem, and midbrain tissue were isolated and analyzed for α-syn, inflammatory markers, and dopaminergic neuronal loss. Gut microbial composition was assessed by 16S rRNA sequencing analysis. Results: We found that local rotenone exposure for 8 weeks did not affect colitis severity and colonic tight junction (TJ) protein expression (ZO-1, Occludin, and Claudin-1). On the other hand, we found that while eight weeks of chronic rotenone administration led to an increase in inflammatory markers, the presence of pre-existing colitis resulted in a considerable change in gut microbiota composition and a decrease in TJ's protein expression. In addition, the administration of rotenone in mice post-colitis caused gastrointestinal function impairment and poor behavioral performances. Itworsened rotenone-induced α-syn pathology in the colon, which extended upward and resulted in severe dopaminergic neuron loss and significant astroglia activation in the dorsal motor nucleus of the vagus (DMV), locus coeruleus, substantia nigra as well as in striatum. Interestingly, in the case of rotenone alone, we found that α-syn induced ChAT+ neuronal death is restricted to the DMV. These findings indicate that long-term rotenone exposure in conjunction with early inflammatory intestinal milieu exacerbates the progression of α-syn pathology and aggravates neurodegeneration in the intragastric mouse PD model. Conclusions: This work provides detailed insight into the involvement of GI inflammation triggered after a neurotoxic insult in the colon and explores their potential to impact central dopaminergic degeneration in PD. This way, we can identify potential therapeutic targets that stop the enteric inflammatory processes involved in progressing PD.

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“…The vagus nerve, which supplies the brain with information from the entire GIT to the left colonic flexure, is generally accepted as the sensor of microbiota metabolites. EECs display a greater diversity and express a variety of proteins that act as signaling molecules on the various targets, both nearby and far away, with some of them demonstrating action in response to a variety of luminal stimuli. , The vagus nerve, the tenth cranial nerve, connects the digestive tract to the brain. It provides nerve endings to the digestive tract, allowing the CNS to control processes like gastric motility .…”

Section: Pathophysiology Associated With Parkinson’s Diseasementioning

confidence: 99%

Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease

Kumari

Taliyan

Dubey

2023

ACS Chem. Neurosci.

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Parkinson’s disease is the second most prevalent neurological disease after Alzheimer’s. Primarily, old age males are more affected than females. The aggregates of oligomeric forms of α-synuclein cause the loss of dopaminergic neurons in the substantia nigra pars compacta. Further, it leads to dopamine shortage in the striatum region. According to recent preclinical studies, environmental factors like pesticides, food supplements, pathogens, etc. enter the body through the mouth or nose and ultimately reach the gut. Further, these factors get accumulated in enteric nervous system which leads to misfolding of α-synuclein gene, and aggregation of this gene results in Lewy pathology in the gut and reaches to the brain through the vagus nerve. This evidence showed a strong bidirectional connection between the gut and the brain, which leads to gastrointestinal problems in Parkinson patients. Moreover, several studies reveal that patients with Parkinson experience more gastrointestinal issues in the early stages of the disease, such as constipation, increased motility, gut inflammation, etc. This review article focuses on the transmission of α-synuclein and the mechanisms involved in the link between the gut and the brain in Parkinson’s disease. Also, this review explores the various pathways involved in Parkinson and current therapeutic approaches for the improvement of Parkinson’s disease.

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

Cited by 14 publications

References 38 publications

Selenium Forms and Dosages Determined Their Biological Actions in Mouse Models of Parkinson’s Disease

Selenium Forms and Dosages Determined Their Biological Actions in Mouse Models of Parkinson’s Disease

Intragastric administration of low-dose rotenone post-colitis exacerbates damage to the nigrostriatal dopaminergic system in Parkinson’s disease: The pace accelerates even more

Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease

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