Vancomycin Pretreatment on MPTP-Induced Parkinson’s Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut

Cui, Chun; Hong, Hui; Shi, Yun; Zhou, Yu; Qiao, Chen-Meng; Zhao, Wenjin; Zhao, Liping; Wu, Jian; Quan, Wei; Niu, Gu-Yu; Wu, Yibo; Li, Chao-Sheng; Cheng, Li; Hong, Yan; Shen, Yan‐Qin

doi:10.1007/s11481-021-10047-y

Cited by 26 publications

(42 citation statements)

References 60 publications

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“…In PD animal models, tetracyclines conferred DA neuroprotection via its anti-inflammatory, anti-oxidant and anti-apoptotic activities, doxycycline can reduce the production of mitochondrial-derived reactive oxygen species and prevent the aggregation and seeding of recombinant α-synuclein, rats exposed to rotenone-induced motor deficits can be improved by minocycline, which increased TH expression and inhibited the release of ROS and NO in the SN ( Sun et al, 2019 ; Dominguez-Meijide et al, 2021 ; Rahmani et al, 2022 ). Recently, another MPTP-induced PD mice model study showed that, in pole and traction tests, mice with motor dysfunction significantly improved after receiving vancomycin as a pretreatment, which could inhibit the metabolism of DA, and vancomycin pretreatment also can alleviate neuroinflammation and decrease the expression of TLR4/MyD88/NF-κB/TNF-α signaling pathway in both brain and gut through reducing the number of astrocytes and microglial cells in the (SNpc) ( Cui et al, 2022 ). However, on the other hand, the use of antibiotics caused antibiotic resistance increased in bacterial pathogens, which could make antibiotics ineffective in treating bacterial infections in the body.…”

Section: Introductionmentioning

confidence: 99%

Effects of levodopa on gut bacterial antibiotic resistance in Parkinson’s disease rat

Sheng

Li²,

Zhao³

et al. 2023

Front. Aging Neurosci.

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The second most prevalent neurodegenerative ailment, Parkinson’s disease (PD), is characterized by both motor and non-motor symptoms. Levodopa is the backbone of treatment for PD at the moment. However, levodopa-induced side effects, such as dyskinesia, are commonly seen in PD patients. Recently, several antibiotics were found to present neuroprotective properties against neurodegenerative and neuro-inflammatory processes, which might be developed to effective therapies against PD. In this study, we aimed to identify if levodopa treatment could influence the gut bacterial antibiotic resistance in PD rat. Fecal samples were collected from healthy rats and 6-OHDA induced PD rats treated with different doses of levodopa, metagenomic sequencing data showed that levodopa resulted in gut bacteria composition change, the biomarkers of gut bacteria analyzed by LEfSe changed as well. More interestingly, compared with levodopa (5 mg/kg)-treated or no levodopa-treated PD rats, levodopa (10 mg/kg) caused a significant decrease in the abundance of tetW and vanTG genes in intestinal bacteria, which were related to tetracycline and vancomycin resistance, while the abundance of AAC6-lb-Suzhou gene increased apparently, which was related to aminoglycosides resistance, even though the total quantity of Antibiotic Resistance Gene (ARG) and Antibiotic Resistance Ontology (ARO) among all groups did not significantly differ. Consequently, our results imply that the combination of levodopa and antibiotics, such as tetracycline and vancomycin, in the treatment of PD may decrease the amount of corresponding antibiotic resistance genes in gut bacteria, which would give a theoretical basis for treating PD with levodopa combined with tetracycline and vancomycin in the future.

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Section: Introductionmentioning

confidence: 99%

Effects of levodopa on gut bacterial antibiotic resistance in Parkinson’s disease rat

Sheng

Li²,

Zhao³

et al. 2023

Front. Aging Neurosci.

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“…Altering the microbiome in α-synuclein overexpressing (ASO) mice modulates brain pathology and motor performance ( Sampson et al, 2016 ), and gut bacterial species have been shown to accelerate disease in other PD mouse models ( Choi et al, 2018 ; Sampson et al, 2020 ). Additionally, antibiotic treatment improves motor symptoms in several models of PD ( Cui et al, 2022 ; Pu et al, 2019 ; Sampson et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice

Abdel-Haq

Schlachetzki

Boktor

et al. 2022

eLife

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Parkinson's disease (PD) is a movement disorder characterized by neuroinflammation, α-synuclein pathology, and neurodegeneration. Most cases of PD are non-hereditary, suggesting a strong role for environmental factors, and it has been speculated that disease may originate in peripheral tissues such as the gastrointestinal (GI) tract before affecting the brain. The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, though mechanisms of gut-brain interactions remain incompletely defined. Intestinal bacteria ferment dietary fibers into short-chain fatty acids, with fecal levels of these molecules differing between PD and healthy controls and in mouse models. Among other effects, dietary microbial metabolites can modulate activation of microglia, brain-resident immune cells implicated in PD. We therefore investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. Feeding a prebiotic high-fiber diet attenuates motor deficits and reduces α-synuclein aggregation in the substantia nigra of mice. Concomitantly, the gut microbiome of ASO mice adopts a profile correlated with health upon prebiotic treatment, which also reduces microglial activation. Single-cell RNA-seq analysis of microglia from the substantia nigra and striatum uncovers increased pro-inflammatory signaling and reduced homeostatic responses in ASO mice compared to wild-type counterparts on standard diets. However, prebiotic feeding reverses pathogenic microglial states in ASO mice and promotes expansion of protective disease-associated macrophage (DAM) subsets of microglia. Notably, depletion of microglia using a CSF1R inhibitor eliminates the beneficial effects of prebiotics by restoring motor deficits to ASO mice despite feeding a prebiotic diet. These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD.

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“…Similar results have been reported in other studies. For instance, Cui demonstrated that vancomycin pretreatment ameliorated motor dysfunction in MPTP-induced PD mice [50]. Another study found that the aggregation of alpha-syn and motor de cits was improved in mice with gut microbiota destruction by antibiotics [51].…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture alleviates motor dysfunction and gut barrier damage by modulating intestinal NLRP3 inflammasome in MPTP-induced Parkinson's disease mice

Guo

Jiang

Yang

et al. 2023

Preprint

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Parkinson’s disease (PD) is a neurodegenerative disorder commonly accompanied by motor dysfunction. Electroacupuncture (EA) has shown anti-inflammatory and neuroprotective effects, although the potential mechanisms remain unclear. We speculated that EA could ameliorate the motor dysfunction of PD and that this would be associated with its regulatory impact on the intestinal microbiota. We applied 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model. EA at the GV16, LR3, and ST36 acupoints was administrated for 12 consecutive days. The results of the open-field test indicated that EA alleviated depression and behavioral defects in PD mice. Further study showed that EA upregulated the expressions of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), and blocked the accumulation of α-synuclein (α-syn) in the midbrain. Additionally, EA increased the mRNA levels of neurotrophic factors like BDNF and GDNF. Moreover, EA prevented the damage to intestinal tissues of PD mice, indicative of suppressed NLRP3 inflammasome activation and increased gut barrier integrity. Notably, the antibiotic-treated mouse experiment validated that the gut microbiota was critical in alleviating PD dyskinesia and intestinal inflammation by EA. In conclusion, our study demonstrated that EA intervention could improve PD by alleviating behavioral defects and gut barrier damage, which provides novel insights into the pathogenesis of PD and its therapy.

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Vancomycin Pretreatment on MPTP-Induced Parkinson’s Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut

Cited by 26 publications

References 60 publications

Effects of levodopa on gut bacterial antibiotic resistance in Parkinson’s disease rat

Effects of levodopa on gut bacterial antibiotic resistance in Parkinson’s disease rat

A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice

Electroacupuncture alleviates motor dysfunction and gut barrier damage by modulating intestinal NLRP3 inflammasome in MPTP-induced Parkinson's disease mice

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