scholarly journals Probiotic Enhancement of Antioxidant Capacity and Alterations of Gut Microbiota Composition in 6-Hydroxydopamin-Induced Parkinson’s Disease Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1823
Author(s):  
Shu-Ping Tsao ◽  
Bira Arumndari Nurrahma ◽  
Ravi Kumar ◽  
Chieh-Hsi Wu ◽  
Tu-Hsueh Yeh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Antioxidant Capacity ◽  
Gut Microbiome ◽  
Dopaminergic Neurons ◽  
Fecal Microbiota ◽  
Antioxidant Enzyme Activities ◽  
Microbiota Composition ◽  
Indirect Pathway

Oxidative stress plays a key role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD), which may be aggravated by concomitant PD-associated gut dysbiosis. Probiotics and prebiotics are therapeutically relevant to these conditions due to their antioxidant, anti-inflammatory, and gut microbiome modulation properties. However, the mechanisms by which probiotic/prebiotic supplementation affects antioxidant capacity and the gut microbiome in PD remains poorly characterized. In this study, we assessed the effects of a Lactobacillus salivarius AP-32 probiotic, a prebiotic (dried AP-32 culture medium supernatant), and a probiotic/prebiotic cocktail in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced PD. The neuroprotective effects and levels of oxidative stress were evaluated after eight weeks of daily supplementation. Fecal microbiota composition was analyzed by fecal 16S rRNA gene sequencing. The supplements were associated with direct increases in host antioxidant enzyme activities and short-chain fatty acid production, protected dopaminergic neurons, and improved motor functions. The supplements also altered the fecal microbiota composition, and some specifically enriched commensal taxa correlated positively with superoxide dismutase, glutathione peroxidase, and catalase activity, indicating supplementation also promotes antioxidant activity via an indirect pathway. Therefore, L. salivarius AP-32 supplementation enhanced the activity of host antioxidant enzymes via direct and indirect modes of action in rats with 6-OHDA-induced PD.

scholarly journals Blood Exosomes Have Neuroprotective Effects in a Mouse Model of Parkinson’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ting Sun ◽  
Zhe-Xu Ding ◽  
Xin Luo ◽  
Qing-Shan Liu ◽  
Yong Cheng
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Amino Acid ◽  
Dopaminergic Neurons ◽  
Motor Coordination ◽  
Oxidized Lipids ◽  
Metabolomic Analysis ◽  
Neuroprotective Effects ◽  
And Control

Parkinson’s disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.

scholarly journals Demonstration of brain region-specific neuronal vulnerability in human iPSC-based model of familial Parkinson’s disease

2020 ◽  
Vol 29 (7) ◽  
pp. 1180-1191
Author(s):  
Razvan-Marius Brazdis ◽  
Julian E Alecu ◽  
Daniel Marsch ◽  
Annika Dahms ◽  
Katrin Simmnacher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Region ◽  
Neuronal Death ◽  
Dopaminergic Neurons ◽  
Control Individual ◽  
Projection Neurons ◽  
Cortical Projection ◽  
Human Ipscs

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor symptoms. While other brain regions also undergo pathologic changes in PD, the relevance of α-Syn aggregation for the preferential loss of mDANs in PD pathology is not completely understood yet. To elucidate the mechanisms of the brain region-specific neuronal vulnerability in PD, we modeled human PD using human-induced pluripotent stem cells (iPSCs) from familial PD cases with a duplication (Dupl) of the α-Syn gene (SNCA) locus. Human iPSCs from PD Dupl patients and a control individual were differentiated into mDANs and cortical projection neurons (CPNs). SNCA dosage increase did not influence the differentiation efficiency of mDANs and CPNs. However, elevated α-Syn pathology, as revealed by enhanced α-Syn insolubility and phosphorylation, was determined in PD-derived mDANs compared with PD CPNs. PD-derived mDANs exhibited higher levels of reactive oxygen species and protein nitration levels compared with CPNs, which might underlie elevated α-Syn pathology observed in mDANs. Finally, increased neuronal death was observed in PD-derived mDANs compared to PD CPNs and to control mDANs and CPNs. Our results reveal, for the first time, a higher α-Syn pathology, oxidative stress level, and neuronal death rate in human PD mDANs compared with PD CPNs from the same patient. The finding implies the contribution of pathogenic α-Syn, probably induced by oxidative stress, to selective vulnerability of substantia nigra dopaminergic neurons in human PD.

scholarly journals Neuroprotective Effects of Lindleyin on Hydrogen Peroxide-Induced Cell Injury and MPTP-Induced Parkinson’s Disease in C57BL/6 Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jin-Jie Zhang ◽  
Xiao-Rong Shi ◽  
Wen-Wen Lv ◽  
Xiao-Long Zhou ◽  
Ying-Dong Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Hydrogen Peroxide ◽  
Parkinson's Disease ◽  
Cell Injury ◽  
In Vivo Studies ◽  
Antioxidant Enzyme Activities ◽  
Apoptotic Pathway ◽  
Neuroprotective Effects

Oxidative stress (OS) is a crucial factor influencing the development of Parkinson’s disease (PD). Here we first reported that Lindleyin (Lin), one of the major components of rhubarb, possessed neuroprotective effects against H2O2-induced SH-SY5Y cell injury and MPTP-induced PD of C57BL/6 mice. The results showed that Lin can decrease cell death and apoptotic rate induced by H2O2 through inhibiting mitochondrial apoptotic pathway and increasing the activities of SOD, GSH-Px, and CAT as well as decreasing the level of MDA. In addition, in vivo studies showed that oral administration of Lin (5 or 20 mg/kg) showed significant change in motor function deficits, antioxidant enzyme activities, apoptotic pathway, and tyrosine hydroxylase expression. Our results reveal that Lin might be a promising anti-PD agent by reducing OS and apoptosis.

scholarly journals Dysfunction of mitochondria as the basis of Parkinson’s disease

2018 ◽  
Vol 6 (4) ◽  
pp. 174-181
Author(s):  
Małgorzata Popis
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Dopaminergic Neurons ◽  
Genetic Factors ◽  
Lewy Bodies ◽  
Main Ingredient ◽  
Mitochondrial Dynamic ◽  
Factors Affecting

AbstractParkinson's disease is the second most common neurodegenerative disease, affecting about 0,15-0,3% of the world's population. Its characteristic feature is a loss of dopaminergic neurons in the substantia nigra. PD leads to dopamine deficiency and formation of intracellular inclusions called Lewy bodies, whose main ingredient is α-synuclein. Other types of nervous system cells are also affected by changes associated with that disease. The underlying molecular pathogenesis involves multiple pathways and mechanisms: mitochondrial function, oxidative stress, genetic factors, α-synuclein proteostasis, mitochondrial dynamic impairment, and disorders of the mitophagy process. This review summarizes the factors affecting the functioning of the mitochondria and their connection to the development of Parkinson's disease.

scholarly journals Lipid-Mediated Oxidative Stress and Inflammation in the Pathogenesis of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Tahira Farooqui ◽  
Akhlaq A. Farooqui
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Platelet Activating Factor ◽  
Lipid Mediators ◽  
Unknown Etiology ◽  
Oxygen Species ◽  
Progressive Loss ◽  
Progressive Neurodegeneration

Parkinson's disease (PD) is a neurodegenerative movement disorder of unknown etiology. PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, depletion of dopamine in the striatum, abnormal mitochondrial and proteasomal functions, and accumulation ofα-synuclein that may be closely associated with pathological and clinical abnormalities. Increasing evidence indicates that both oxidative stress and inflammation may play a fundamental role in the pathogenesis of PD. Oxidative stress is characterized by increase in reactive oxygen species (ROS) and depletion of glutathione. Lipid mediators for oxidative stress include 4-hydroxynonenal, isoprostanes, isofurans, isoketals, neuroprostanes, and neurofurans. Neuroinflammation is characterized by activated microglial cells that generate proinflammatory cytokines, such as TNF-αand IL-1β. Proinflammatory lipid mediators include prostaglandins and platelet activating factor, together with cytokines may play a prominent role in mediating the progressive neurodegeneration in PD.

scholarly journals An altered microbiome in a Parkinson’s disease model Drosophila melanogaster has a negative effect on development

2021 ◽  
Author(s):  
Jade Parker-Character ◽  
David R. Hager ◽  
Tanner B. Call ◽  
Zachary S. Pickup ◽  
Scott A. Turnbull ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Disease Model ◽  
Model Organism ◽  
Fecal Microbiota ◽  
Microbiota Composition ◽  
Host Genotype ◽  
Negative Effect ◽  
And Control

Abstract It is well-established that there are differences in the fecal microbiota composition between Parkinson’s disease (PD) patients and control populations, but the mechanisms underlying these differences are not yet fully understood. To begin to close the gap between description and mechanism we studied the relationship between the microbiota and PD in a model organism, Drosophila melanogaster. First, fecal transfers were performed with a D. melanogaster model of PD that had a mutation in the parkin (park25) gene. Results indicate that the PD model feces had a negative effect on both pupation and eclosion in both control and park25 flies, with a greater effect in PD model flies. Analysis of the microbiota composition revealed differences between the control and park25 flies, consistent with many human studies. Conversely, gnotobiotic treatment of axenic embryos with feces-derived bacterial cultures did not affect eclosure. We speculate this result might be due to similarities in bacterial prevalence between mutant and control feces. Further, we confirmed a bacteria-potentiated impact on mutant and control fly phenotypes by measuring eclosure rate in park25flies that were mono-associated with members of the fly microbiota. Both the fecal transfer and the mono-association results indicate a host genotype-microbiota interaction. Overall, this study concludes functional effects of the fly microbiota on PD model flies, providing support to the developing body of knowledge regarding the influence of the microbiota on PD.

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