Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway

2022 ◽  
Author(s):  
Ning Wang ◽  
Bainian Feng ◽  
Bin Hu ◽  
Yuliang Cheng ◽  
Yahui Guo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Echinacea Purpurea ◽  
Tlr4 Signaling ◽  
Chicoric Acid ◽  
Purple Coneflower ◽  
Tlr4 Signaling Pathway

Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (Echinacea purpurea), has been regarded as nutraceutical to combat inflammation, virus and obesity. Parkinson’s Disease (PD) is a...

scholarly journals Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhe Zhao ◽  
Jingwen Ning ◽  
Xiu-qi Bao ◽  
Meiyu Shang ◽  
Jingwei Ma ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Deficits ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway ◽  
The Brain ◽  
Gut Microbiota Dysbiosis

Abstract Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis. Results We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon. Conclusions Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis.

TLR4 signaling mediates AP-1 activation in an MPTP-induced mouse model of Parkinson's disease

2016 ◽  
Vol 32 ◽  
pp. 96-102 ◽  
Author(s):  
Xu-Dong Zhao ◽  
Fa-Xiang Wang ◽  
Wen-Fu Cao ◽  
Yong-Hong Zhang ◽  
Yan Li
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Tlr4 Signaling

scholarly journals 7,8-dihydroxyflavone ameliorates motor deficits via regulating autophagy in MPTP-induced mouse model of Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Li Zuo ◽  
Chunfang Dai ◽  
Lilin Yi ◽  
Zhifang Dong
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Dopaminergic Neurons ◽  
Motor Deficits ◽  
Autophagic Flux ◽  
Therapeutic Effects ◽  
Ampk Signaling ◽  
N2a Cells

AbstractParkinson’s disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra and diminished dopamine content in the striatum. Recent reports show that 7,8-dihydroxyflavone (DHF), a TrkB agonist, attenuates the α-synuclein deposition and ameliorates motor deficits. However, the underlying mechanism is unclear. In this study, we investigated whether autophagy is involved in the clearance of α-synuclein and the signaling pathway through which DHF exerts therapeutic effects. We found that the administration of DHF (5 mg/kg/day, i.p.) prevented the loss of dopaminergic neurons and improved motor functions in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, whereas these protective effects of DHF were completely blocked by autophagy inhibitor chloroquine (CQ). Further in vitro studies showed that autophagy was inhibited in N2A cells treated with 1-methyl-4-phenylpyridinium (MPP+), as reflected by a significant decrease in the expressions of autophagy marker proteins (Beclin1 and LC3II) and an increase in the expression of autophagic flux marker p62. DHF restored the impaired autophagy to control level in MPP+-treated N2A cells by inhibiting the ERK-LKB1-AMPK signaling pathway. Taken together, these results demonstrate that DHF exerts therapeutic effects in MPTP/MPP+-induced neurotoxicity by inhibiting the ERK-LKB1-AMPK signaling pathway and subsequently improving impaired autophagy.

scholarly journals Transcriptomic Profiling of Circular RNA in Different Brain Regions of Parkinson’s Disease in a Mouse Model

2020 ◽  
Vol 21 (8) ◽  
pp. 3006 ◽  
Author(s):  
Erteng Jia ◽  
Ying Zhou ◽  
Zhiyu Liu ◽  
Liujing Wang ◽  
Tinglan Ouyang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Brain Regions ◽  
Differentially Expressed ◽  
Sequencing Analysis ◽  
Qrt Pcr

Parkinson’s disease (PD) is the second most common neurodegenerative disease and although many studies have been done on this disease, the underlying mechanisms are still poorly understood and further studies are warranted. Therefore, this study identified circRNA expression profiles in the cerebral cortex (CC), hippocampus (HP), striatum (ST), and cerebellum (CB) regions of the 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model using RNA sequencing (RNA-seq), and differentially expressed circRNA were validated using reverse transcription quantitative real-time PCR (qRT-PCR). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and competing endogenous RNA (ceRNA) network analyses were also performed to explore the potential function of circRNAs. The results show that, compared with the control group, 24, 66, 71, and 121 differentially expressed circRNAs (DE-circRNAs) were found in the CC, HP, ST, and CB, respectively. PDST vs. PDCB, PDST vs. PDHP, and PDCB vs. PDHP groups have 578, 110, and 749 DE-circRNAs, respectively. Then, seven DE-cirRNAs were selected for qRT-PCR verification, where the expressions were consistent with the sequencing analysis. The GO and KEGG pathway analyses revealed that these DE-circRNAs participate in several biological functions and signaling pathways, including glutamic synapse, neuron to neuron synapse, cell morphogenesis involved in neuron differentiation, Parkinson’s disease, axon guidance, cGMP-PKG signaling pathway, and PI3K-Akt signaling pathway. Furthermore, the KEGG analysis of the target genes predicted by DE-circRNAs indicated that the target genes predicted by mmu_circRNA_0003292, mmu_circRNA_0001320, mmu_circRNA_0005976, and mmu_circRNA_0005388 were involved in the PD-related pathway. Overall, this is the first study on the expression profile of circRNAs in the different brain regions of PD mouse model. These results might facilitate our understanding of the potential roles of circRNAs in the pathogenesis of PD. Moreover, the results also indicate that the mmu_circRNA_0003292-miRNA-132-Nr4a2 pathway might be involved in the regulation of the molecular mechanism of Parkinson’s disease.

scholarly journals Dahuang Zexie Decoction Protects against High-Fat Diet-Induced NAFLD by Modulating Gut Microbiota-Mediated Toll-Like Receptor 4 Signaling Activation and Loss of Intestinal Barrier

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jing Fang ◽  
Xiaoqi Sun ◽  
Boyu Xue ◽  
Nanyuan Fang ◽  
Min Zhou
Keyword(s):  
Gut Microbiota ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
Intestinal Barrier ◽  
Toll Like Receptor ◽  
High Fat ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway ◽  
Signaling Activation

Increasing evidence suggests that intestinal dysbiosis, intestinal barrier dysfunction, and activated Toll-like receptor 4 (TLR4) signaling play key roles in the pathogenesis of NAFLD. Dahuang Zexie Decoction (DZD) has been verified to be effective for treating NAFLD, but the mechanisms remain unclear. In this study, we investigated the effects of DZD on NAFLD rats and determined whether such effects were associated with change of the gut microbiota, downregulated activity of the TLR4 signaling pathway, and increased expressions of tight junction (TJ) proteins in the gut. Male Sprague Dawley rats were fed high-fat diet (HFD) for 16 weeks to induce NAFLD and then given DZD intervention for 4 weeks. We found that DZD reduced body and liver weights of NAFLD rats, improved serum lipid levels and liver function parameters, and relieved NAFLD. We further found that DZD changed intestinal bacterial communities, inhibited the intestinal TLR4 signaling pathway, and restored the expressions of TJ proteins in the gut. Meanwhile ten potential components of DZD had been identified. These findings suggest that DZD may protects against NAFLD by modulating gut microbiota-mediated TLR4 signaling activation and loss of intestinal barrier. However, further studies are needed to clarify the mechanism by which DZD treats NAFLD.

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