Dopaminergic Neurodegeneration in Cultivated with

Overview

Journal MicroPubl Biol

Date 2025 Jan 22

PMID 39839711

Authors

Edward F Griffin

Madeline G Owens

Affiliations

Soon will be listed here.

Abstract

Disruption of the human microbiome has emerged as a major contributing factor in the etiology of neurodegenerative disease. Previous work suggests a positive correlation between periodontal inflammation and Parkinson's disease. Here, we show that feeding animals causes neurodegeneration that is not additive with neurodegeneration induced by the Parkinson's-associated protein, α-synuclein. In contrast, α-synuclein-expressing animals fed show additional disruption in basal slowing, suggesting that induces neurodegeneration while altering neuronal function of extant neurons. Though the mechanism is unclear, these results suggest a relationship between and neurodegeneration that warrants further investigation.

References

Singleton A, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J . alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003; 302(5646):841. DOI: 10.1126/science.1090278. View

Sheets S, Potempa J, Travis J, Fletcher H, Casiano C . Gingipains from Porphyromonas gingivalis W83 synergistically disrupt endothelial cell adhesion and can induce caspase-independent apoptosis. Infect Immun. 2006; 74(10):5667-78. PMC: 1594922. DOI: 10.1128/IAI.01140-05. View

Kim S, Kwon S, Kam T, Panicker N, Karuppagounder S, Lee S . Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019; 103(4):627-641.e7. PMC: 6706297. DOI: 10.1016/j.neuron.2019.05.035. View

Williams G, Schonhoff A, Jurkuvenaite A, Gallups N, Standaert D, Harms A . CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson's disease. Brain. 2021; 144(7):2047-2059. PMC: 8370411. DOI: 10.1093/brain/awab103. View

Boisvert H, Duncan M . Clathrin-dependent entry of a gingipain adhesin peptide and Porphyromonas gingivalis into host cells. Cell Microbiol. 2008; 10(12):2538-52. PMC: 3016922. DOI: 10.1111/j.1462-5822.2008.01228.x. View

Griffin E, Yan X, Caldwell K, Caldwell G . Distinct functional roles of Vps41-mediated neuroprotection in Alzheimer's and Parkinson's disease models of neurodegeneration. Hum Mol Genet. 2018; 27(24):4176-4193. PMC: 6276837. DOI: 10.1093/hmg/ddy308. View

Jungbauer G, Stahli A, Zhu X, Auber Alberi L, Sculean A, Eick S . Periodontal microorganisms and Alzheimer disease - A causative relationship?. Periodontol 2000. 2022; 89(1):59-82. PMC: 9314828. DOI: 10.1111/prd.12429. View

Zeng Y, Wu T, Liang F, Long S, Guo W, Huang Y . Expression of human Ras-related protein Rab39B variant T168K in leads to motor dysfunction and dopaminergic neuron degeneration. Heliyon. 2024; 10(5):e26902. PMC: 10912484. DOI: 10.1016/j.heliyon.2024.e26902. View

Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A . In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol Dis. 2005; 21(2):404-12. DOI: 10.1016/j.nbd.2005.08.002. View

10.

Polymeropoulos M, Lavedan C, Leroy E, Ide S, Dehejia A, Dutra A . Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997; 276(5321):2045-7. DOI: 10.1126/science.276.5321.2045. View

11.

Martinez B, Caldwell K, Caldwell G . C. elegans as a model system to accelerate discovery for Parkinson disease. Curr Opin Genet Dev. 2017; 44:102-109. DOI: 10.1016/j.gde.2017.02.011. View

12.

Kim H, Perentis R, Caldwell G, Caldwell K . Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson's models. Cell Death Dis. 2018; 9(5):555. PMC: 5945629. DOI: 10.1038/s41419-018-0619-5. View

13.

Nakajima M, Arimatsu K, Kato T, Matsuda Y, Minagawa T, Takahashi N . Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver. PLoS One. 2015; 10(7):e0134234. PMC: 4517782. DOI: 10.1371/journal.pone.0134234. View

14.

Campos-Acuna J, Elgueta D, Pacheco R . T-Cell-Driven Inflammation as a Mediator of the Gut-Brain Axis Involved in Parkinson's Disease. Front Immunol. 2019; 10:239. PMC: 6384270. DOI: 10.3389/fimmu.2019.00239. View

15.

Sawin E, Ranganathan R, Horvitz H . C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron. 2000; 26(3):619-31. DOI: 10.1016/s0896-6273(00)81199-x. View

16.

Adams B, Nunes J, Page M, Roberts T, Carr J, Nell T . Parkinson's Disease: A Systemic Inflammatory Disease Accompanied by Bacterial Inflammagens. Front Aging Neurosci. 2019; 11:210. PMC: 6718721. DOI: 10.3389/fnagi.2019.00210. View

17.

Trindade D, Carvalho R, Machado V, Chambrone L, Mendes J, Botelho J . Prevalence of periodontitis in dentate people between 2011 and 2020: A systematic review and meta-analysis of epidemiological studies. J Clin Periodontol. 2023; 50(5):604-626. DOI: 10.1111/jcpe.13769. View

18.

Bornhorst J, Chakraborty S, Meyer S, Lohren H, Grosse Brinkhaus S, Knight A . The effects of pdr1, djr1.1 and pink1 loss in manganese-induced toxicity and the role of α-synuclein in C. elegans. Metallomics. 2014; 6(3):476-90. PMC: 3954834. DOI: 10.1039/c3mt00325f. View

19.

Caldwell K, Tucci M, Armagost J, Hodges T, Chen J, Memon S . Investigating bacterial sources of toxicity as an environmental contributor to dopaminergic neurodegeneration. PLoS One. 2009; 4(10):e7227. PMC: 2751819. DOI: 10.1371/journal.pone.0007227. View

20.

Hamamichi S, Rivas R, Knight A, Cao S, Caldwell K, Caldwell G . Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model. Proc Natl Acad Sci U S A. 2008; 105(2):728-33. PMC: 2206604. DOI: 10.1073/pnas.0711018105. View