Agathobaculum butyriciproducens Shows Neuroprotective Effects in a 6-OHDAInduced Mouse Model of Parkinson’s Disease

다국어 초록 (Multilingual Abstract)

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the association between alterations in PD pathology and the gut microbiota has been explored. Microbiota-targeted interventions have been suggested as a novel therapeutic approach for PD. Agathobaculum butyriciproducens SR79T (SR79) is an anaerobic bacterium. Previously, we showed that SR79 treatment induced cognitive improvement and reduced Alzheimer's disease pathologies in a mouse model. In this study, we hypothesized that SR79 treatment may have beneficial effects on PD pathology. To investigate the therapeutic effects of SR79 on PD, 6-hydroxydopamine (6-OHDA)- induced mouse models were used. D-Amphetamine sulfate (d-AMPH)-induced behavioral rotations and dopaminergic cell death were analyzed in unilateral 6-OHDA-lesioned mice. Treatment with SR79 significantly decreased ipsilateral rotations induced by d-AMPH. Moreover, SR79 treatment markedly activated the AKT/GSK3β signaling pathway in the striatum. In addition, SR79 treatment affected the Nrf2/ARE signaling pathway and its downstream target genes in the striatum of 6- OHDA-lesioned mice. Our findings suggest a protective role of SR79 in 6-OHDA-induced toxicity by regulating the AKT/Nrf2/ARE signaling pathway and astrocyte activation. Thus, SR79 may be a potential microbe-based intervention and therapeutic strategy for PD.

참고문헌 (Reference)

1 Rani L, "Unravelling the role of gut microbiota in Parkinson's disease progression : Pathogenic and therapeutic implications" 168 : 100-112, 2021

2 Haavik J, "Tyrosine hydroxylase and Parkinson's disease" 16 : 285-309, 1998

3 Xu R, "The role of the probiotic Akkermansia muciniphila in brain functions : insights underpinning therapeutic potential" 11 : 1-26, 2022

4 Yang L, "The role of insulin/IGF-1/PI3K/Akt/GSK3beta signaling in Parkinson's disease dementia" 12 : 73-, 2018

5 Keith BJ, "The mouse brain in stereotaxic coordinates, Third edition Ed" Elsevier 2007

6 Cryan JF, "The microbiota-gut-brain Axis" 99 : 1877-2013, 2019

7 Martinez-Martin P, "The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's disease" 26 : 399-406, 2011

8 Jope RS, "The glamour and gloom of glycogen synthase kinase-3" 29 : 95-102, 2004

9 Albin RL, "The functional anatomy of basal ganglia disorders" 12 : 366-375, 1989

10 Ansari F, "The effects of probiotics and prebiotics on mental disorders : A review on depression, anxiety, alzheimer, and autism spectrum disorders" 21 : 555-565, 2020

11 Stevens B, "The classical complement cascade mediates CNS synapse elimination" 131 : 1164-1178, 2007

12 Susanne Fonseca Santos, "The Gut and Parkinson's Disease—A Bidirectional Pathway" Frontiers Media SA 10 : 2019

13 Liu J, "Sodium butyrate exerts protective effect against Parkinson's disease in mice via stimulation of glucagon like peptide-1" 381 : 176-181, 2017

14 Unger MM, "Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls" 32 : 66-72, 2016

15 Miao L, "Regulation of superoxide dismutase genes : implications in disease" 47 : 344-356, 2009

16 Neufeld KM, "Reduced anxiety-like behavior and central neurochemical change in germ-free mice" 23 : 255-264, 2011

17 Liddelow SA, "Reactive astrocytes : Production, function, and therapeutic potential" 46 : 957-967, 2017

18 de Oliveira MR, "Protective effect of carnosic acid against paraquat-induced redox impairment and mitochondrial dysfunction in SH-SY5Y cells : Role for PI3K/Akt/Nrf2 pathway" 32 : 41-54, 2016

19 Srivastav S, "Probiotics mixture increases butyrate, and subsequently rescues the nigral dopaminergic neurons from MPTP and rotenone-induced neurotoxicity" 69 : 73-86, 2019

20 Hsieh TH, "Probiotics alleviate the progressive deterioration of motor functions in a mouse model of Parkinson's disease" 10 : 206-, 2020

21 Aaseth J, "Prevention of progression in Parkinson's disease" 31 : 737-747, 2018

22 Cantu-Jungles TM, "Potential of prebiotic butyrogenic fibers in Parkinson's disease" 10 : 663-, 2019

23 Go J, "Piperlongumine decreases cognitive impairment and improves hippocampal function in aged mice" 42 : 1875-1884, 2018

24 Rana AQ, "Parkinson's disease : a review of non-motor symptoms" 15 : 549-562, 2015

25 Kalia LV, "Parkinson's disease" 386 : 896-912, 2015

26 Franke TF, "PI3K : downstream AKTion blocks apoptosis" 88 : 435-437, 1997

27 Quesada A, "PI3 kinase/Akt activation mediates estrogen and IGF-1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson's disease" 68 : 632-644, 2008

28 Percario S, "Oxidative stress in Parkinson's disease : Potential benefits of antioxidant supplementation" 2020 : 2360872-, 2020

29 Reiter RJ, "Oxidative damage in the central nervous system : protection by melatonin" 56 : 359-384, 1998

30 Zhu Y, "Overview of tyrosine hydroxylase in Parkinson's disease" 11 : 350-358, 2012

31 Oh YJ, "Overexpression of Bcl-2 attenuates MPP+, but not 6-ODHA, induced cell death in a dopaminergic neuronal cell line" 2 : 157-167, 1995

32 Troncoso-Escudero P, "Outside in : Unraveling the role of neuroinflammation in the progression of Parkinson's disease" 9 : 860-, 2018

33 Bruce-Keller AJ, "Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity" 77 : 607-615, 2015

34 Li L, "Nrf2/ARE pathway activation, HO-1 and NQO1 induction by polychlorinated biphenyl quinone is associated with reactive oxygen species and PI3K/AKT signaling" 209 : 56-67, 2014

35 Schapira AHV, "Non-motor features of Parkinson disease" 18 : 435-450, 2017

36 Liddelow SA, "Neurotoxic reactive astrocytes are induced by activated microglia" 541 : 481-487, 2017

37 Hirsch EC, "Neuroinflammation in Parkinson's disease : a target for neuroprotection?" 8 : 382-397, 2009

38 Whitton PS, "Neuroinflammation and the prospects for anti-inflammatory treatment of Parkinson's disease" 11 : 788-794, 2010

39 Deumens R, "Modeling Parkinson's disease in rats : an evaluation of 6-OHDA lesions of the nigrostriatal pathway" 175 : 303-317, 2002

40 Ryu YK, "Metformin regulates astrocyte reactivity in Parkinson's disease and normal aging" 175 : 108173-, 2020

41 Ryu YK, "Metformin inhibits the development of L-DOPA-induced dyskinesia in a murine model of Parkinson's disease" 55 : 5715-5726, 2018

42 Glinka Y, "Mechanism of 6-hydroxydopamine neurotoxicity" 50 : 55-66, 1997

43 Park HY, "Inhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson's disease" 34 : 11744-11753, 2014

44 Xie CL, "Inhibition of Glycogen Synthase Kinase-3beta(GSK-3beta)as potent therapeutic strategy to ameliorates L-dopa-induced dyskinesia in 6-OHDA parkinsonian rats" 6 : 23527-, 2016

45 Yan J, "Inflammatory response in Parkinson's disease(Review)" 10 : 2223-2233, 2014

46 Krishnankutty A, "In vivo regulation of glycogen synthase kinase 3beta activity in neurons and brains" 7 : 8602-, 2017

47 Braak H, "Idiopathic Parkinson's disease : possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen" 110 : 517-536, 2003

48 Park TS, "Humulus japonicus inhibits the progression of Alzheimer's disease in a APP/PS1 transgenic mouse model" 39 : 21-30, 2017

49 류영경 ; 강영 ; 고준 ; 박혜연 ; 노정란 ; 김용훈 ; 황정환 ; 최동희 ; 한상섭 ; 오원근 ; 이철호 ; 김경심, "Humulus japonicus Prevents Dopaminergic Neuron Death in 6-Hydroxydopamine-Induced Models of Parkinson’s Disease" 한국식품영양과학회 20 (20): 116-123, 2017

50 Go J, "Human gut microbiota Agathobaculum butyriciproducens improves cognitive impairment in LPS-induced and APP/PS1 mouse models of Alzheimer's disease" 86 : 96-108, 2021

51 Nicholson JK, "Host-gut microbiota metabolic interactions" 336 : 1262-1267, 2012

52 Kawase T, "Gut microbiota of mice putatively modifies amino acid metabolism in the host brain" 117 : 775-783, 2017

53 Zheng P, "Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism" 21 : 786-796, 2016

54 Fulling C, "Gut microbe to brain signaling : What happens in vagus" 101 : 998-1002, 2019

55 Chen G, "Glycogen synthase kinase 3beta(GSK3beta)mediates 6-hydroxydopamineinduced neuronal death" 18 : 1162-1164, 2004

56 Cersosimo MG, "Gastrointestinal manifestations in Parkinson's disease : prevalence and occurrence before motor symptoms" 260 : 1332-1338, 2013

57 Fasano A, "Gastrointestinal dysfunction in Parkinson's disease" 14 : 625-639, 2015

58 Park HY, "Gadd45beta ameliorates L-DOPA-induced dyskinesia in a Parkinson's disease mouse model" 89 : 169-179, 2016

59 Doble BW, "GSK-3 : tricks of the trade for a multi-tasking kinase" 116 : 1175-1186, 2003

60 Hongli Huang, "Fecal microbiota transplantation to treat Parkinson's disease with constipation" Ovid Technologies (Wolters Kluwer Health) 98 (98): e16163-, 2019

61 Zhao Z, "Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiotagut-brain axis" 9 : 226-, 2021

62 Sun J, "Fecal microbiota transplantation alleviated Alzheimer's disease-like pathogenesis in APP/PS1 transgenic mice" 9 : 189-, 2019

63 Castelli V, "Effects of the probiotic formulation SLAB51 in in vitro and in vivo Parkinson's disease models" 12 : 4641-4659, 2020

64 Holscher HD, "Dietary fiber and prebiotics and the gastrointestinal microbiota" 8 : 172-184, 2017

65 Aleyasin H, "DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway" 107 : 3186-3191, 2010

66 Everard A, "Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity" 110 : 9066-9071, 2013

67 Claesson MJ, "Composition, variability, and temporal stability of the intestinal microbiota of the elderly" 108 (108): 4586-4591, 2011

68 Keshavarzian A, "Colonic bacterial composition in Parkinson's disease" 30 : 1351-1360, 2015

69 Thiruvengadam M, "Bioactive compounds in oxidative stress-mediated diseases : Targeting the NRF2/ARE signaling pathway and epigenetic regulation" 10 : 1859-, 2021

70 Beaulieu JM, "Beyond cAMP : The regulation of Akt and GSK3 by dopamine receptors" 4 : 38-, 2011

71 Gorshkov K, "Astrocytes as targets for drug discovery" 23 : 673-680, 2018

72 Gagne JJ, "Anti-inflammatory drugs and risk of Parkinson disease : a meta-analysis" 74 : 995-1002, 2010

73 Chung CY, "An endogenous serine/threonine protein phosphatase inhibitor, G-substrate, reduces vulnerability in models of Parkinson's disease" 27 : 8314-8323, 2007

74 Kramer BC, "Alterations in the cellular distribution of bcl-2, bcl-x and bax in the adult rat substantia nigra following striatal 6-hydroxydopamine lesions" 33 : 213-223, 2004

75 Ahn S, "Agathobaculum butyriciproducens gen. nov.  sp. nov., a strict anaerobic, butyrate-producing gut bacterium isolated from human faeces and reclassification of Eubacterium desmolans as Agathobaculum desmolans comb. nov" 66 : 3656-3661, 2016

76 Hughes AJ, "Accuracy of clinical diagnosis of idiopathic Parkinson's disease : a clinicopathological study of 100 cases" 55 : 181-184, 1992

77 Hayashi A, "A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice" 13 : 711-722, 2013