Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson’s Disease
Open accessAbstract
Analysis of human pathology led Braak to postulate that α-synuclein (α-syn) pathology could spread from the gut to brain via the vagus nerve. Here, we test this postulate by assessing α-synucleinopathy in the brain in a novel gut-to-brain α-syn transmission mouse model, where pathological α-syn preformed fibrils were injected into the duodenal and pyloric muscularis layer. Spread of pathologic α-syn in brain, as assessed by phosphorylation of serine 129 of α-syn, was observed first in the dorsal motor nucleus, then in caudal portions of the hindbrain, including the locus coeruleus, and much later in basolateral amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta. Moreover, loss of dopaminergic neurons and motor and non-motor symptoms were observed in a similar temporal manner. Truncal vagotomy and α-syn deficiency prevented the gut-to-brain spread of α-synucleinopathy and associated neurodegeneration and behavioral deficits. This study supports the Braak hypothesis in the etiology of idiopathic Parkinson's disease (PD).
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Cellular and animal studies have provided a model for prion-like spread of α-synuclein from the gut to the brain via the enteric nervous system, chiefly through the vagus nerve.
“Third, cellular and animal studies have provided a model for prion-like spread of α-synuclein from the gut to the brain via the enteric nervous system, chiefly through the vagus nerve [15–17].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [16]
Vagotomy can prevent the transmission of pathological a-synuclein to the CNS in animal models.
“Vagotomy can prevent the transmission of pathological a-synuclein to the CNS in animal models.137,138”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [137]
Truncal vagotomy prevents the spread of α-syn from the gut to the brain, which is associated with neurodegeneration and behavioural deficits.
“Correspondingly, truncal vagotomy prevents the spread of α-syn from the gut to the brain, which is associated with neurodegeneration and behavioural deficits.241,242”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [241]
The pathology of PD might begin in the gut and gradually progress to the brain.
“Braak et al. theorized that the pathology of PD might begin in the gut and gradually progress to the brain [14], which was partially supported by subsequent research [15]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [15]
Gut injection with α-synuclein fibrils (12.5 μg) in mice systematically spread pathology upwards to the dorsal motor nucleus of the vagus, locus coeruleus, amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta, and induced motor and non-motor symptoms resembling Parkinson's disease.
“Gut injection with α-synuclein fibrils (12.5 μg) in mice also systematically spread pathology “upwards”, i.e., to the dorsal motor nucleus of the vagus, locus coeruleus, amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta, and it induced motor and non-motor symptoms resembling Parkinson's disease [401].”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [401]
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Cites
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · see citing works
Morris water maze: procedures for assessing spatial and related forms of learning and memory
Vorhees, C. V., & Williams, M. T. (2006) · Nature Protocols · doi:10.1038/nprot.2006.116 · Cited by 4,629 · see citing works
Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.018 · Cited by 3,622 · see citing works
The tail suspension test: A new method for screening antidepressants in mice
Steru, L., Chermat, R., Thierry, B., & Simon, P. (1985) · Psychopharmacology · doi:10.1007/bf00428203 · Cited by 3,534 · see citing works
Behavioural despair in rats: A new model sensitive to antidepressant treatments
Porsolt, R. D., Anton, G., Blavet, N., & Jalfre, M. (1978) · European Journal of Pharmacology · doi:10.1016/0014-2999(78)90118-8 · Cited by 3,138 · see citing works
Stages in the development of Parkinson’s disease-related pathology
Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0956-9 · Cited by 2,689 · see citing works
Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M.-Y. (2012) · Science · doi:10.1126/science.1227157 · Cited by 2,563 · see citing works
α-Synuclein is phosphorylated in synucleinopathy lesions
Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M., Shen, J., Takio, K., & Iwatsubo, T. (2002) · Nature Cell Biology · doi:10.1038/ncb748 · Cited by 1,906 · see citing works
Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment
Chaudhuri, К. R., & Schapira, A. H. V. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70068-7 · Cited by 1,739 · see citing works
Braak, H., R�b, U., Gai, W. P., & Del Tredici, K. (2003) · Journal of Neural Transmission · doi:10.1007/s00702-002-0808-2 · Cited by 1,683 · see citing works
Cryan, J. F., Mombereau, C., & Vassout, A. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.009 · Cited by 1,674 · see citing works
The enteric nervous system and neurogastroenterology
Furness, J. B. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.32 · Cited by 1,619 · see citing works
Volpicelli-Daley, L. A., Luk, K. C., Patel, T. P., Tanik, S. A., Riddle, D. M., Stieber, A., Meaney, D. F., Trojanowski, J. Q., & Lee, V. M.-Y. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.033 · Cited by 1,569 · see citing works
Pellow, S., & File, S. E. (1986) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(86)90552-6 · Cited by 1,534 · see citing works
Anderson, J. P., Walker, D., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J., Barbour, R., Huang, J., Kling, K., Lee, M., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600933200 · Cited by 1,418 · see citing works
Role of Escherichia coli Curli Operons in Directing Amyloid Fiber Formation
Chapman, M., Robinson, L. S., Pinkner, J., Roth, R., Heuser, J., Hammar, M., Normark, S., & Hultgren, S. (2002) · Science · doi:10.1126/science.1067484 · Cited by 1,282 · see citing works
Bevins, R. A., & Besheer, J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.205 · Cited by 1,278 · see citing works
Whole-Brain Mapping of Direct Inputs to Midbrain Dopamine Neurons
Watabe‐Uchida, M., Zhu, L., Ogawa, S. K., Vamanrao, A., & Uchida, N. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.017 · Cited by 1,221 · see citing works
Selective neuronal vulnerability in Parkinson disease
Surmeier, D. J., Obeso, J. A., & Halliday, G. M. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.178 · Cited by 1,120 · see citing works
Assessing nest building in mice
Deacon, R. M. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.170 · Cited by 1,115 · see citing works
Parkinson's disease: a dual‐hit hypothesis
Hawkes, C. H., Del Tredici, K., & Braak, H. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00874.x · Cited by 1,021 · see citing works
Gastrointestinal Dysfunction in Parkinson’s Disease
Fasano, A., Visanji, N. P., Liu, L. W. C., Lang, A. E., & Pfeiffer, R. F. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00007-1 · Cited by 1,016 · see citing works
Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic
Ressler, K. J., & Mayberg, H. S. (2007) · Nature Neuroscience · doi:10.1038/nn1944 · Cited by 1,007 · see citing works
Forsyth, C. B., Shannon, K. M., Kordower, J. H., Voigt, R. M., Shaikh, M., Jaglin, J. A., Estes, J. D., Dodiya, H. B., & Keshavarzian, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028032 · Cited by 974 · see citing works
Luk, K. C., Song, C., O’Brien, P., Stieber, A., Branch, J. R., Brunden, K. R., Trojanowski, J. Q., & Lee, V. M. ‐. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908005106 · Cited by 958 · see citing works
Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats
Holmqvist, S., Chutna, O., Bousset, L., Aldrin-Kirk, P., Li, W., Björklund, T., Wang, Z.-Y., Roybon, L., Melki, R., & Li, J.-Y. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1343-6 · Cited by 925 · see citing works
Gastrointestinal dysfunction in Parkinson's disease
Pfeiffer, R. F. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00307-7 · Cited by 925 · see citing works
Direct and indirect pathways of basal ganglia: a critical reappraisal
Calabresi, P., Picconi, B., Tozzi, A., Ghiglieri, V., & Filippo, M. D. (2014) · Nature Neuroscience · doi:10.1038/nn.3743 · Cited by 820 · see citing works
Vagotomy and subsequent risk of <scp>P</scp> arkinson's disease
Svensson, E., Horváth‐Puhó, E., Thomsen, R. W., Djurhuus, J. C., Pedersen, L., Borghammer, P., & Sørensen, H. T. (2015) · Annals of Neurology · doi:10.1002/ana.24448 · Cited by 806 · see citing works
Idiopathic hyposmia as a preclinical sign of Parkinson's disease
Ponsen, M. M., Stoffers, D., Booij, J., van Eck‐Smit, B. L. F., Wolters, E. C., & Berendse, H. W. (2004) · Annals of Neurology · doi:10.1002/ana.20160 · Cited by 741 · see citing works
Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3
Mao, X., Ou, M. T., Karuppagounder, S. S., Kam, T., Yin, X., Xiong, Y., Ge, P., Umanah, G. K. E., Brahmachari, S., Shin, J., et al. (2016) · Science · doi:10.1126/science.aah3374 · Cited by 739 · see citing works
Self-citationVolpicelli-Daley, L. A., Luk, K. C., & Lee, V. M.-Y. (2014) · Nature Protocols · doi:10.1038/nprot.2014.143 · Cited by 731 · see citing works
Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs
Forman, M. S., Trojanowski, J. Q., & Lee, V. M.-Y. (2004) · Nature Medicine · doi:10.1038/nm1113 · Cited by 715 · see citing works
Pathogenesis of Parkinson disease—the gut–brain axis and environmental factors
Klingelhoefer, L., & Reichmann, H. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.197 · Cited by 598 · see citing works
Pan-Montojo, F., Anichtchik, O., Dening, Y., Knels, L., Pursche, S., Jung, R., Jackson, S., Gille, G., Spillantini, M. G., Reichmann, H., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008762 · Cited by 524 · see citing works
Early and Progressive Sensorimotor Anomalies in Mice Overexpressing Wild-Type Human α-Synuclein
Fleming, S. M., Salcedo, J. D., Fernagut, P., Rockenstein, E. M., Masliah, E., Levine, M. S., & Chesselet, M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3080-04.2004 · Cited by 477 · see citing works
Vagotomy and Parkinson disease: A Swedish register–based matched-cohort study
Liu, B., Fang, F., Pedersen, N. L., Tillander, A., Ludvigsson, J. F., Ekbom, A., Svenningsson, P., Chen, H., & Wirdefeldt, K. (2017) · Neurology · doi:10.1212/wnl.0000000000003961 · Cited by 447 · see citing works
Guo, J. L., Narasimhan, S., Changolkar, L., He, Z., Stieber, A., Zhang, B., Gathagan, R. J., Iba, M., McBride, J. D., Trojanowski, J. Q., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20160833 · Cited by 440 · see citing works
Pan-Montojo, F., Schwarz, M., Winkler, C., Arnhold, M., O'Sullivan, G. A., Pal, A., Said, J., Marsico, G., Verbavatz, J.-M., Rodrigo-Angulo, M., et al. (2012) · Scientific Reports · doi:10.1038/srep00898 · Cited by 405 · see citing works
Rey, N. L., Steiner, J. A., Maroof, N., Luk, K. C., Madaj, Z., Trojanowski, J. Q., Lee, V. M. ‐., & Brundin, P. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160368 · Cited by 389 · see citing works
Topography of efferent vagal innervation of the rat gastrointestinal tract
Berthoud, H., Carlson, N. R., & Powley, T. L. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.260.1.r200 · Cited by 363 · see citing works
Multiple organ involvement by alpha-synuclein pathology in lewy body disorders
Gelpi, E., Navarro‐Otano, J., Tolosa, E., Gaig, C., Compta, Y., Rey, M. J., Martí, M. J., Hernández, I., Valldeoriola, F., Reñé, R., et al. (2014) · Movement Disorders · doi:10.1002/mds.25776 · Cited by 361 · see citing works
Emotional, cognitive and neurochemical alterations in a premotor stage model of Parkinson's disease
Tadaiesky, M. T., Dombrowski, P. A., Figueiredo, C. P., Cargnin‐Ferreira, E., Cunha, C. D., & Takahashi, R. N. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.08.035 · Cited by 342 · see citing works
Uemura, N., Yagi, H., Uemura, M. T., Hatanaka, Y., Yamakado, H., & Takahashi, R. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0257-5 · Cited by 328 · see citing works
Braak, H., Sastre, M., Böhl, J., de Vos, R. A. I., & Tredici, K. D. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0193-x · Cited by 320 · see citing works
Cell-to-cell transmission of non-prion protein aggregates
Lee, S., Desplats, P., Sigurdson, C. J., Tsigelny, I. F., & Masliah, E. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.145 · Cited by 307 · see citing works
Self-citationParkinson's Disease: The Dual Hit Theory Revisited
Hawkes, C. H., Del Tredici, K., & Braak, H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04365.x · Cited by 303 · see citing works
Kuo, Y., Li, Z., Jiao, Y., Gaborit, N., Pani, A. K., Orrison, B. M., Bruneau, B. G., Giasson, B. I., Smeyne, R. J., Gershon, M. D., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq038 · Cited by 288 · see citing works
Karuppagounder, S. S., Brahmachari, S., Lee, Y., Dawson, V. L., Dawson, T. M., & Ko, H. S. (2014) · Scientific Reports · doi:10.1038/srep04874 · Cited by 264 · see citing works
Vagotomy Dissociates Short- and Long-Term Controls of Circulating Ghrelin
Williams, D. L., Grill, H. J., Cummings, D. E., & Kaplan, J. M. (2003) · Endocrinology · doi:10.1210/en.2003-1059 · Cited by 260 · see citing works
Santiago, R. M., Barbieiro, J., Lima, M. M. S., Dombrowski, P. A., Andreatini, R., & Vital, M. A. B. F. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.06.004 · Cited by 251 · see citing works
Caudo‐rostral brain spreading of α‐synuclein through vagal connections
Ulusoy, A., Rusconi, R., Pérez‐Revuelta, B. I., Musgrove, R. E., Helwig, M., Winzen‐Reichert, B., & Monte, D. A. D. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201302475 · Cited by 250 · see citing works
α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease
Chandra, R., Hiniker, A., Kuo, Y.-M., Nussbaum, R. L., & Liddle, R. A. (2017) · JCI Insight · doi:10.1172/jci.insight.92295 · Cited by 236 · see citing works
Noradrenaline and Parkinson's Disease
Delaville, C., Deurwaerdère, P. D., & Benazzouz, A. (2011) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2011.00031 · Cited by 229 · see citing works
Olfactory deficits in mice overexpressing human wildtype α‐synuclein
Fleming, S. M., Tetreault, N. A., Mulligan, C. K., Hutson, C. B., Masliah, E., & Chesselet, M. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06346.x · Cited by 209 · see citing works
Manfredsson, F. P., Luk, K. C., Benskey, M. J., Gezer, A., Garcia, J., Kuhn, N. C., Sandoval, I. M., Patterson, J. R., O'Mara, A., Yonkers, R., et al. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.01.008 · Cited by 199 · see citing works
Behavioral phenotyping of mouse models of Parkinson's disease
Taylor, T. N., Greene, J. G., & Miller, G. W. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.03.004 · Cited by 198 · see citing works
Miyoshi, E., Wietzikoski, S., Camplessei, M., Silveira, R., Takahashi, R. N., & Cunha, C. D. (2002) · Brain Research Bulletin · doi:10.1016/s0361-9230(02)00754-2 · Cited by 164 · see citing works
Wakabayashi, K., Mori, F., Tanji, K., Orimo, S., & Takahashi, H. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0706-x · Cited by 156 · see citing works
The vagus nerve modulates BDNF expression and neurogenesis in the hippocampus
O’Leary, O. F., Ogbonnaya, E. S., Felice, D., Levone, B. R., C. Conroy, L., Fitzgerald, P., Bravo, J. A., Forsythe, P., Bienenstock, J., Dinan, T. G., et al. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2017.12.004 · Cited by 139 · see citing works
Afferent projections to the dorsal motor nucleus of the vagus
Roges, R. C., Kita, H., Butcher, L. L., et al. (1980) · Brain Research Bulletin · doi:10.1016/s0361-9230(80)80006-2 · Cited by 126 · see citing works
Marinho-Buzelli, A. R., Bonnyman, A. M., & Verrier, M. C. (2014) · Clinical Rehabilitation · doi:10.1177/0269215514556297 · Cited by 125 · see citing works
Microbial colonization is required for normal neurobehavioral development in zebrafish
Phelps, D. W., Brinkman, N. E., Keely, S. P., Anneken, E. M., Catron, T. R., Betancourt, D. A., Wood, C. E., Espenschied, S. T., Rawls, J. F., & Tal, T. L. (2017) · Scientific Reports · doi:10.1038/s41598-017-10517-5 · Cited by 120 · see citing works
Loganin improves learning and memory impairments induced by scopolamine in mice
Kwon, S., Kim, H., Lee, S., & Jang, C. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.06.062 · Cited by 118 · see citing works
Self-citationThe Effect of Fragmented Pathogenic α-Synuclein Seeds on Prion-like Propagation
Tarutani, A., Suzuki, G., Shimozawa, A., Nonaka, T., Akiyama, H., Hisanaga, S.-I., & Hasegawa, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.734707 · Cited by 118 · see citing works
Cunha, C. D., Angelucci, M. E. M., Canteras, N. S., Wonnacott, S., & Takahashi, R. N. (2002) · Cellular and Molecular Neurobiology · doi:10.1023/a:1020736131907 · Cited by 105 · see citing works
Wu, C., Lien, C., Hou, W., Chiang, P., & Tsai, K. (2016) · Scientific Reports · doi:10.1038/srep27358 · Cited by 105 · see citing works
Does vagotomy reduce the risk of Parkinson's disease?
Tysnes, O., Kenborg, L., Herlofson, K., Steding‐Jessen, M., Horn, A., Olsen, J. H., & Reichmann, H. (2015) · Annals of Neurology · doi:10.1002/ana.24531 · Cited by 102 · see citing works
Transmission of α-synuclein seeds in neurodegenerative disease: recent developments
Karpowicz, R. J., Trojanowski, J. Q., & Lee, V. M. ‐. (2019) · Laboratory Investigation · doi:10.1038/s41374-019-0195-z · Cited by 102 · see citing works
Lack of promoter IV‐driven BDNF transcription results in depression‐like behavior
Sakata, K., Jin, L., & Jha, S. (2010) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2010.00605.x · Cited by 95 · see citing works
The "serotonin hypothesis" for depression in Parkinson's disease.
Mayeux, R. P. (1990) · PubMed · Cited by 88 · see citing works
Sensitive Assessment of Hippocampal Learning Using Temporally Dissociated Passive Avoidance Task
Eagle, A. L., Wang, H., & Robison, A. J. (2016) · BIO-PROTOCOL · doi:10.21769/bioprotoc.1821 · Cited by 76 · see citing works
Assessments of plasma ghrelin levels in the early stages of Parkinson's disease
Song, N., Wang, W., Jia, F., Du, X., Xie, A., He, Q., Shen, X., Zhang, J., Rogers, J. T., Xie, J., et al. (2017) · Movement Disorders · doi:10.1002/mds.27095 · Cited by 67 · see citing works
Locus coeruleus projections to the dorsal motor vagus nucleus in the rat
Horst, G. J. T., Toes, G. J., & van Willigen, J. D. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90111-z · Cited by 57 · see citing works
Lewy body dementia and Parkinson’s disease with dementia
Dodel, R. C., Csóti, I., Ebersbach, G., Fuchs, G., Hahne, M., Kuhn, W., Oechsner, M., Jost, W. H., Reichmann, H., & Schulz, J. B. (2008) · Journal of Neurology · doi:10.1007/s00415-008-5007-0 · Cited by 55 · see citing works
Changes in the immune system in depression and dementia: causal or coincidental effects?
Leonard, B. E., & Myint, A.-M. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.2/bleonard · Cited by 51 · see citing works
Vagotomy attenuates bleomycin-induced pulmonary fibrosis in mice
Song, N., Liu, J., Shaheen, S. P., Du, L., Proctor, M., Roman, J., & Yu, J. (2015) · Scientific Reports · doi:10.1038/srep13419 · Cited by 47 · see citing works
Villageliú, D. N., Rasmussen, S., & Lyte, M. (2018) · FEMS Microbiology Ecology · doi:10.1093/femsec/fiy096 · Cited by 40 · see citing works
Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction Kinetics in Mice
Talaga, A. K., Dong, F. N., Reisert, J., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0392-17.2017 · Cited by 37 · see citing works
Sariñana, J., & Tonegawa, S. (2015) · Hippocampus · doi:10.1002/hipo.22492 · Cited by 29 · see citing works
Arias, N., Méndez, M., & Arias, J. L. (2015) · Hippocampus · doi:10.1002/hipo.22430 · Cited by 23 · see citing works
El‐Salhy, M., Danielsson, A., Axelsson, H., et al. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(99)00107-x · Cited by 22 · see citing works
Learning deficits in rats overexpressing the dopamine transporter
Bernhardt, N. R., Lieser, M. K., Hlusicka, E. B., Habelt, B., Wieske, F., Edemann-Callesen, H., Garthe, A., & Winter, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-32608-7 · Cited by 15 · see citing works
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Cryan, J. F., O'Riordan, K. J., Sandhu, K., Peterson, V., & Dinan, T. G. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30356-4 · Cited by 1,336 · see citing works
The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders
Socała, K., Doboszewska, U., Szopa, A., Serefko, A., Włodarczyk, M., Zielińska, A., Poleszak, E., Fichna, J., & Wlaź, P. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105840 · Cited by 857 · see citing works
NAD+ in Brain Aging and Neurodegenerative Disorders
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.001 · Cited by 790 · see citing works
Inflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications
Pajares, M., I. Rojo, A., Manda, G., Boscá, L., & Cuadrado, A. (2020) · Cells · doi:10.3390/cells9071687 · Cited by 779 · see citing works
Parkinson disease and the immune system - Associations, mechanisms and therapeutics
Tan, E.-K., Chao, Y.-X., West, A., Chan, L.-L., Poewe, W., & Jankovic, J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0344-4 · Cited by 457 · see citing works
A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice
Sampson, T. R., Challis, C., Jain, N., Moiseyenko, A., Ladinsky, M. S., Shastri, G. G., Thron, T., Needham, B. D., Horvath, I., Debelius, J. W., et al. (2020) · eLife · doi:10.7554/elife.53111 · Cited by 439 · see citing works
Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice
Challis, C., Hori, A., Sampson, T. R., Yoo, B. B., Challis, R. C., Hamilton, A. M., Mazmanian, S. K., Volpicelli-Daley, L. A., & Gradinaru, V. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0589-7 · Cited by 405 · see citing works
Fecal Microbiota Transplantation in Neurological Disorders
Vendrik, K. E. W., Ooijevaar, R. E., de Jong, P. R. C., Laman, J. D., van Oosten, B. W., van Hilten, J. J., Ducarmon, Q. R., Keller, J. J., Kuijper, E. J., & Contarino, M. F. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00098 · Cited by 413 · see citing works
Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases
Bartels, T., De Schepper, S., & Hong, S. (2020) · Science · doi:10.1126/science.abb8587 · Cited by 412 · see citing works
The microbiome–gut–brain axis in Parkinson disease — from basic research to the clinic
Tan, A. H., Lim, S. Y., & Lang, A. E. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00681-2 · Cited by 392 · see citing works
Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms
Wallen, Z. D., Demirkan, A., Twa, G., Cohen, G., Dean, M. N., Standaert, D. G., Sampson, T. R., & Payami, H. (2022) · Nature Communications · doi:10.1038/s41467-022-34667-x · Cited by 346 · see citing works
The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options
Wang, Q., Luo, Y., Ray Chaudhuri, K., Reynolds, R., Tan, E.-K., & Pettersson, S. (2021) · Brain · doi:10.1093/brain/awab156 · Cited by 281 · see citing works
Anionic nanoplastic contaminants promote Parkinson’s disease–associated α-synuclein aggregation
Liu, Z., Sokratian, A., Duda, A. M., Xu, E., Stanhope, C., Fu, A., Strader, S., Li, H., Yuan, Y., Bobay, B. G., et al. (2023) · Science Advances · doi:10.1126/sciadv.adi8716 · Cited by 262 · see citing works
Chen, S.-J., Chen, C.-C., Liao, H.-Y., Lin, Y.-T., Wu, Y.-W., Liou, J.-M., Wu, M.-S., Kuo, C.-H., & Lin, C.-H. (2022) · Neurology · doi:10.1212/wnl.0000000000013225 · Cited by 269 · see citing works
Wallen, Z. D., Appah, M., Dean, M. N., Sesler, C. L., Factor, S. A., Molho, E., Zabetian, C. P., Standaert, D. G., & Payami, H. (2020) · npj Parkinson s Disease · doi:10.1038/s41531-020-0112-6 · Cited by 252 · see citing works
Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?
Blesa, J., Foffani, G., Dehay, B., Bezard, E., & Obeso, J. A. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00542-9 · Cited by 232 · see citing works
The intestinal barrier in disorders of the central nervous system
Pellegrini, C., Fornai, M., D'Antongiovanni, V., Antonioli, L., Bernardini, N., & Derkinderen, P. (2023) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(22)00241-2 · Cited by 239 · see citing works
The Microbiome as a Modifier of Neurodegenerative Disease Risk
Fang, P., Kazmi, S. A., Jameson, K. G., & Hsiao, E. Y. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.06.008 · Cited by 226 · see citing works
Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates
Arotcarena, M.-L., Dovero, S., Prigent, A., Bourdenx, M., Camus, S., Porras, G., Thiolat, M.-L., Tasselli, M., Aubert, P., Kruse, N., et al. (2020) · Brain · doi:10.1093/brain/awaa096 · Cited by 210 · see citing works
Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study
Xue, L.-J., Yang, X.-Z., Tong, Q., Shen, P., Ma, S.-J., Wu, S.-N., Zheng, J.-L., & Wang, H.-G. (2020) · Medicine · doi:10.1097/md.0000000000022035 · Cited by 186 · see citing works
Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease
Zhu, M., Liu, X., Ye, Y., Yan, X., Cheng, Y., Zhao, L., Chen, F., & Ling, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.937555 · Cited by 177 · see citing works
Rosario, D., Bidkhori, G., Lee, S., Bedarf, J., Hildebrand, F., Le Chatelier, E., Uhlen, M., Ehrlich, S. D., Proctor, G., Wüllner, U., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108807 · Cited by 167 · see citing works
Peterson, C. T. (2020) · Journal of Evidence-Based Integrative Medicine · doi:10.1177/2515690x20957225 · Cited by 160 · see citing works
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease
Li, P., Killinger, B. A., Ensink, E., Beddows, I., Yilmaz, A., Lubben, N., Lamp, J., Schilthuis, M., Vega, I. E., Woltjer, R., et al. (2021) · Metabolites · doi:10.3390/metabo11010029 · Cited by 146 · see citing works
Microbiota–neuroepithelial signalling across the gut–brain axis
Ohara, T. E., & Hsiao, E. Y. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-024-01136-9 · Cited by 147 · see citing works
Diet in Parkinson’s Disease: Critical Role for the Microbiome
Jackson, A., Forsyth, C. B., Shaikh, M., Voigt, R. M., Engen, P. A., Ramirez, V., & Keshavarzian, A. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.01245 · Cited by 145 · see citing works
Inflammatory bowel diseases and Parkinson's disease
Brudek, T. (2019) · Journal of Parkinson’s Disease · doi:10.3233/jpd-191729 · Cited by 139 · see citing works
Bruggeman, A., Vandendriessche, C., Hamerlinck, H., De Looze, D., Tate, D. J., Vuylsteke, M., De Commer, L., Devolder, L., Raes, J., Verhasselt, B., et al. (2024) · eClinicalMedicine · doi:10.1016/j.eclinm.2024.102563 · Cited by 139 · see citing works
Alpha-Synuclein: Mechanisms of Release and Pathology Progression in Synucleinopathies
Brás, I. C., & Outeiro, T. F. (2021) · Cells · doi:10.3390/cells10020375 · Cited by 136 · see citing works
Metta, V., Leta, V., Mrudula, K. R., Prashanth, L. K., Goyal, V., Borgohain, R., Chung-Faye, G., & Chaudhuri, K. R. (2022) · Journal of Neurology · doi:10.1007/s00415-021-10567-w · Cited by 130 · see citing works
The Gut-Brain Axis in Inflammatory Bowel Disease—Current and Future Perspectives
Günther, C., Rothhammer, V., Karow, M., Neurath, M., & Winner, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168870 · Cited by 123 · see citing works
Nishiwaki, H., Ito, M., Hamaguchi, T., Maeda, T., Kashihara, K., Tsuboi, Y., Ueyama, J., Yoshida, T., Hanada, H., Takeuchi, I., et al. (2022) · npj Parkinson's Disease · doi:10.1038/s41531-022-00328-5 · Cited by 116 · see citing works
The Intestinal Barrier in Parkinson’s Disease: Current State of Knowledge
van IJzendoorn, S. C. D., & Derkinderen, P. (2019) · Journal of Parkinson’s Disease · doi:10.3233/jpd-191707 · Cited by 97 · see citing works
Nuzum, N. D., Loughman, A., Szymlek-Gay, E. A., Hendy, A., Teo, W.-P., & Macpherson, H. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.02.003 · Cited by 103 · see citing works
TLR2 and TLR4 in Parkinson’s disease pathogenesis: The environment takes a toll on the gut
Gorecki, A. M., Anyaegbu, C. C., & Anderton, R. S. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00271-0 · Cited by 103 · see citing works
Antibiotic Exposure and Risk of Parkinson's Disease in Finland: A Nationwide Case‐Control Study
Mertsalmi, T. H., Pekkonen, E., & Scheperjans, F. (2020) · Movement Disorders · doi:10.1002/mds.27924 · Cited by 88 · see citing works
Oral and Gut Dysbiosis Leads to Functional Alterations in Parkinson’s Disease
Jo, S., Kang, W., Hwang, Y. S., Lee, S. H., Park, K. W., Kim, M. S., Lee, H., Yoon, H. J., Park, Y. K., Chalita, M., et al. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-022-00351-6 · Cited by 85 · see citing works
Self-citationFeng, Y.-K., Wu, Q.-L., Peng, Y.-W., Liang, F.-Y., You, H.-J., Feng, Y.-W., Li, G., Li, X.-J., Liu, S.-H., Li, Y.-C., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02027-5 · Cited by 87 · see citing works
A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice
Abdel-Haq, R., Schlachetzki, J. C., Boktor, J. C., Cantu-Jungles, T. M., Thron, T., Zhang, M., Bostick, J. W., Khazaei, T., Chilakala, S., Morais, L. H., et al. (2022) · eLife · doi:10.7554/elife.81453 · Cited by 82 · see citing works
The gut-brain axis and Parkinson disease: Clinical and pathogenetic relevance
Menozzi, E., Macnaughtan, J., & Schapira, A. H. V. (2021) · Annals of Medicine · doi:10.1080/07853890.2021.1890330 · Cited by 81 · see citing works
Xie, Z., Zhang, M., Luo, Y., Jin, D., Guo, X., Yang, W., Zheng, J., Zhang, H., Zhang, L., Deng, C., et al. (2023) · Aging and disease · doi:10.14336/ad.2023.0309 · Cited by 80 · see citing works
Wang, H., Chen, G., Ahn, E. H., Xia, Y., Kang, S. S., Liu, X., Liu, C., Han, M.-H., Chen, S., & Ye, K. (2023) · npj Parkinson's Disease · doi:10.1038/s41531-022-00430-8 · Cited by 71 · see citing works
Lorente-Picón, M., & Laguna, A. (2021) · Biomolecules · doi:10.3390/biom11030433 · Cited by 69 · see citing works
Reyes, J. F., Ekmark-Léwen, S., Perdiki, M., Klingstedt, T., Hoffmann, A., Wiechec, E., Nilsson, P., Nilsson, K. P. R., Alafuzoff, I., Ingelsson, M., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01136-3 · Cited by 59 · see citing works
Friedland, R. P., McMillan, J. D., & Kurlawala, Z. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051652 · Cited by 56 · see citing works
Yan, Y., Ren, S., Duan, Y., Lu, C., Niu, Y., Wang, Z., Inglis, B., Ji, W., Zheng, Y., & Si, W. (2021) · npj Biofilms and Microbiomes · doi:10.1038/s41522-021-00242-3 · Cited by 51 · see citing works
Malfertheiner, K., Stefanova, N., & Heras-Garvin, A. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.737195 · Cited by 46 · see citing works
Liu, N., Yang, C., Liang, X., Cao, K., Xie, J., Luo, Q., & Luo, H. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01642-z · Cited by 45 · see citing works
Exploring Human-Genome Gut-Microbiome Interaction in Parkinson’s Disease
Wallen, Z. D., Stone, W. J., Factor, S. A., Molho, E., Zabetian, C. P., Standaert, D. G., & Payami, H. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00218-2 · Cited by 41 · see citing works
Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates
Cosma-Grigorov, A., Meixner, H., Mrochen, A., Wirtz, S., Winkler, J., & Marxreiter, F. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.01041 · Cited by 38 · see citing works
The gut–brain axis in early Parkinson’s disease: from prodrome to prevention
Oliver, P. J., Civitelli, L., & Hu, M. T. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13138-5 · Cited by 42 · see citing works
Liu, D., Guo, J.-J., Su, J.-H., Svanbergsson, A., Yuan, L., Haikal, C., Li, W., Gouras, G., & Li, J.-Y. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00242-5 · Cited by 32 · see citing works
Huntington, T. E., & Srinivasan, R. (2021) · Aging and disease · doi:10.14336/ad.2021.0517 · Cited by 34 · see citing works
Qu, Y., An, K., Wang, D., Yu, H., Li, J., Min, Z., Xiong, Y., Xue, Z., & Mao, Z. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04726-7 · Cited by 30 · see citing works
Post-COVID-19 Parkinsonism and Parkinson’s Disease Pathogenesis: The Exosomal Cargo Hypothesis
Mysiris, D. S., Vavougios, G. D., Karamichali, E., Papoutsopoulou, S., Stavrou, V. T., Papayianni, E., Boutlas, S., Mavridis, T., Foka, P., Zarogiannis, S. G., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179739 · Cited by 25 · see citing works
Chan, D. G., Ventura, K., Villeneuve, A., Du Bois, P., & Holahan, M. R. (2022) · Journal of Parkinson's Disease · doi:10.3233/jpd-223461 · Cited by 24 · see citing works
Drobny, A., Ngo, P. A., Neurath, M. F., Zunke, F., & López-Posadas, R. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.655123 · Cited by 24 · see citing works
Jia, X., Chen, Q., Zhang, Y., & Asakawa, T. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1296713 · Cited by 22 · see citing works
Ji, T., Huang, H., Liu, J., Peng, T., Zhou, X., Tan, Q., Yuan, J., Hua, H., Ding, S., & Liu, H. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14952 · Cited by 17 · see citing works
Grathwohl, S., Quansah, E., Maroof, N., Steiner, J. A., Spycher, L., Benmansour, F., Duran-Pacheco, G., Siebourg-Polster, J., Oroszlan-Szovik, K., Remy, H., et al. (2020) · doi:10.21203/rs.3.rs-100199/v1 · Cited by 17 · see citing works
Dumitru, C. N., Dumitru, A. O., Popa, G. V., Marcu, T., Ursu, M., Nechita, A., & Matei, N. M. (2026) · Dentistry Journal · doi:10.3390/dj14050289 · Cited by 6 · see citing works
“Studies showing that vagotomy prevents the behavioral and neurochemical effects of probiotic administration [72] and attenuates the propagation of alpha-synuclein pathology from the gut to the brain in PD models [75,76] underscore the importance of this pathway.”
- Authors
- Kim, S., Kwon, S.-H., Kam, T.-I., Panicker, N., Karuppagounder, S. S., Lee, S., Lee, J. H., Kim, W. R., Kook, M., Foss, C. A., Shen, C., Lee, H., Kulkarni, S., Pasricha, P. J., Lee, G., Pomper, M. G., Dawson, V. L., Dawson, T. M., & Ko, H. S.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Dawson, Ted M.
- Ko, Han Seok
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 103
- Issue
- 4
- Pages
- 627-641.e7
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC6706297
- OpenAlex
- W2953534538
- Cited by
- 1,397
- References
- 83
- Citations by year
- 2026: 175 · 2025: 205 · 2024: 198 · 2023: 167 · 2022: 224 · 2021: 210 · 2020: 171 · 2019: 47
- FWCI
- 110.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- JPB Foundation
- National Institutes of Health
- Adrienne Helis Malvin Medical Research Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Parkinson's disease, alpha-synuclein, vagus nerve, Braak hypothesis, preformed fibrils, serine 129 phosphorylation, dorsal motor nucleus of the vagus, locus coeruleus, substantia nigra pars compacta, dopaminergic neuron loss, vagotomy, mouse model, neurodegeneration, motor and non-motor symptoms
- MeSH terms
- Animals, Axonal Transport, Brain Chemistry, Duodenum, Humans, Injections, Intramuscular, Memory Disorders, Mice, Inbred C57BL, Models, Neurological, Muscle, Smooth, Nesting Behavior, Phosphorylation, Protein Processing, Post-Translational, Pylorus, Vagotomy, Vagus Nerve, Lewy Bodies, Mice, Knockout, Maze Learning, Parkinsonian Disorders, Rotarod Performance Test, Mice, alpha-Synuclein, Dopaminergic Neurons, Protein Aggregates
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