Multimodal Image Technologies Investigate the Role and Mechanism of Probiotics in Improving RBD with Parkinson's Disease

Summary

Rapid eye movement sleep behavior disorder (RBD) is important non-movement feature, and also the important risk factor of Parkinson's disease (PD). In our previous work, we found that the movement features and RBD of PD patients improved after taking probiotics. The later was not reported before and the mechanism not clear. To investigate its role and mechanism, we plan to enroll patients of PD-RBD, idiopathic RBD, and healthy control, collect data of multimodal image technology before and after probiotic treatment，including resting state functional MRI，1H-MRS，123I-MIBG; analyze these data with clinical features, including UPDRS -III score, RBD-HK score , as well as the bacteria abundance and level of glutamate，GABA in blood and stool. Then, construct PD mouse model by fecal transplantation of PD patient, give or not give mouse probiotics treatment, and detect the level of glutamate, GABA, and so on, as well as α-synuclein of each brain area of each group, to explore the role and mechanism of probiotics in improving RBD and movement disorder of PD.

Timeline

Start

2022-09-01

Primary completion

2025-06-01

Completion

2025-06-30

Publications

• Background Valencia Garcia S, Libourel PA, Lazarus M, Grassi D, Luppi PH, Fort P. Genetic inactivation of glutamate neurons in the rat sublaterodorsal tegmental nucleus recapitulates REM sleep behaviour disorder. Brain. 2017 Feb;140(2):414-428. doi: 10.1093/brain/aww310. Epub 2016 Dec 21.
• Background Henrich MT, Geibl FF, Lee B, Chiu WH, Koprich JB, Brotchie JM, Timmermann L, Decher N, Matschke LA, Oertel WH. A53T-alpha-synuclein overexpression in murine locus coeruleus induces Parkinson's disease-like pathology in neurons and glia. Acta Neuropathol Commun. 2018 May 10;6(1):39. doi: 10.1186/s40478-018-0541-1.
• Background Knudsen K, Fedorova TD, Hansen AK, Sommerauer M, Otto M, Svendsen KB, Nahimi A, Stokholm MG, Pavese N, Beier CP, Brooks DJ, Borghammer P. In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study. Lancet Neurol. 2018 Jul;17(7):618-628. doi: 10.1016/S1474-4422(18)30162-5. Epub 2018 Jun 1.
• Background Pyatigorskaya N, Gaurav R, Arnaldi D, Leu-Semenescu S, Yahia-Cherif L, Valabregue R, Vidailhet M, Arnulf I, Lehericy S. Magnetic Resonance Imaging Biomarkers to Assess Substantia Nigra Damage in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. Sleep. 2017 Nov 1;40(11). doi: 10.1093/sleep/zsx149.
• Background Mayer G, Bitterlich M, Kuwert T, Ritt P, Stefan H. Ictal SPECT in patients with rapid eye movement sleep behaviour disorder. Brain. 2015 May;138(Pt 5):1263-70. doi: 10.1093/brain/awv042. Epub 2015 Mar 1.
• Background Rahayel S, Postuma RB, Montplaisir J, Bedetti C, Brambati S, Carrier J, Monchi O, Bourgouin PA, Gaubert M, Gagnon JF. Abnormal Gray Matter Shape, Thickness, and Volume in the Motor Cortico-Subcortical Loop in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: Association with Clinical and Motor Features. Cereb Cortex. 2018 Feb 1;28(2):658-671. doi: 10.1093/cercor/bhx137.
• Background De Marzi R, Seppi K, Hogl B, Muller C, Scherfler C, Stefani A, Iranzo A, Tolosa E, Santamaria J, Gizewski E, Schocke M, Skalla E, Kremser C, Poewe W. Loss of dorsolateral nigral hyperintensity on 3.0 tesla susceptibility-weighted imaging in idiopathic rapid eye movement sleep behavior disorder. Ann Neurol. 2016 Jun;79(6):1026-30. doi: 10.1002/ana.24646. Epub 2016 Apr 22.
• Background Rolinski M, Griffanti L, Piccini P, Roussakis AA, Szewczyk-Krolikowski K, Menke RA, Quinnell T, Zaiwalla Z, Klein JC, Mackay CE, Hu MT. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease. Brain. 2016 Aug;139(Pt 8):2224-34. doi: 10.1093/brain/aww124. Epub 2016 Jun 12.
• Background Luppi PH. Jouvet's animal model of RBD, clinical RBD, and their relationships to REM sleep mechanisms. Sleep Med. 2018 Sep;49:28-30. doi: 10.1016/j.sleep.2018.05.026. Epub 2018 Jun 6.
• Background Alam R, Abdolmaleky HM, Zhou JR. Microbiome, inflammation, epigenetic alterations, and mental diseases. Am J Med Genet B Neuropsychiatr Genet. 2017 Sep;174(6):651-660. doi: 10.1002/ajmg.b.32567. Epub 2017 Jul 10.
• Background Fang X. Potential role of gut microbiota and tissue barriers in Parkinson's disease and amyotrophic lateral sclerosis. Int J Neurosci. 2016 Sep;126(9):771-6. doi: 10.3109/00207454.2015.1096271. Epub 2015 Oct 16.
• Background Stolzenberg E, Berry D, Yang D, Lee EY, Kroemer A, Kaufman S, Wong GCL, Oppenheim JJ, Sen S, Fishbein T, Bax A, Harris B, Barbut D, Zasloff MA. A Role for Neuronal Alpha-Synuclein in Gastrointestinal Immunity. J Innate Immun. 2017;9(5):456-463. doi: 10.1159/000477990. Epub 2017 Jun 27.
• Background Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016 Dec 1;167(6):1469-1480.e12. doi: 10.1016/j.cell.2016.11.018.
• Background Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord. 2015 Mar;30(3):350-8. doi: 10.1002/mds.26069. Epub 2014 Dec 5.

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