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Lactiplantibacillus plantarum PS128 Alleviates Exaggerated Cortical Beta Oscillations and Motor Deficits in the 6-Hydroxydopamine Rat Model of Parkinson’s Disease

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by midbrain dopaminergic neuronal loss and subsequent physical impairments. Levodopa manages symptoms best, while deep brain stimulation (DBS) is effective for advanced PD patients; however, side effects occur with the diminishing therapeutic window. Recently, Lactiplantibacillus plantarum PS128 (PS128) was found to elevate dopamine levels in rodent brains, suggesting its potential to prevent PD. Here, the therapeutic efficacy of PS128 was examined in the 6-hydroxydopamine rat PD model. Suppression of the power spectral density of beta oscillations (beta PSD) in the primary motor cortex (M1) was recorded as the indicator of disease progression. We found that 6 weeks of daily PS128 supplementation suppressed M1 beta PSD as well as did levodopa and DBS. Long-term normalization of M1 beta PSD was found in PS128-fed rats, whereas levodopa and DBS showed only temporal effects. PS128 + levodopa and PS128 + DBS exhibited better therapeutic effects than did levodopa + DBS or either alone. Significantly improved motor functions in PS128-fed rats were correlated with normalization of M1 beta PSD. Brain tissue analyses further demonstrated the role of PS128 in dopaminergic neuroprotection and the enhanced availability of neurotransmitters. These findings suggest that psychobiotic PS128 might be used alongside conventional therapies to treat PD patients.

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Data Availability

The data presented in this study are available on request from the corresponding author.

References

  1. Tritsch NX, Ding JB, Sabatini BL (2012) Dopaminergic neurons inhibit striatal output through non-canonical release of GABA. Nature 490:262–266. https://doi.org/10.1038/nature11466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Woodruff GN, Kelly PH, Elkhawad AO (1976) Effects of dopamine receptor stimulants on locomotor activity of rats with electrolytic or 6-hydroxydopamine-induced lesions of the nucleus accumbens. Psychopharmacologia 47:195–198. https://www.ncbi.nlm.nih.gov/pubmed/1273217

  3. Murer MG, Moratalla R (2011) Striatal signaling in L-DOPA-induced dyskinesia: common mechanisms with drug abuse and long term memory involving D1 dopamine receptor stimulation. Front Neuroanat 5:51. https://doi.org/10.3389/fnana.2011.00051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mugge L, Krafcik B, Pontasch G, Alnemari A, Neimat J, Gaudin D (2019) A review of biomarkers use in Parkinson with deep brain stimulation: a successful past promising a bright future. World Neurosurg 123:197–207. https://doi.org/10.1016/j.wneu.2018.11.247

    Article  PubMed  Google Scholar 

  5. Temel Y, Kessels A, Tan S, Topdag A, Boon P, Visser-Vandewalle V (2006) Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review. Parkinsonism Relat Disord 12:265–272. https://doi.org/10.1016/j.parkreldis.2006.01.004

    Article  PubMed  Google Scholar 

  6. Little S, Brown P (2014) The functional role of beta oscillations in Parkinson’s disease. Parkinsonism Relat Disord 20:S44–S48. https://doi.org/10.1016/s1353-8020(13)70013-0

    Article  PubMed  Google Scholar 

  7. Holt AB, Kormann E, Gulberti A, Potter-Nerger M, McNamara CG, Cagnan H, Baaske MK, Little S, Koppen JA, Buhmann C et al (2019) Phase-dependent suppression of beta oscillations in Parkinson’s disease patients. J Neurosci 39:1119–1134. https://doi.org/10.1523/JNEUROSCI.1913-18.2018

    Article  PubMed  PubMed Central  Google Scholar 

  8. Galvan A, Devergnas A, Wichmann T (2015) Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state. Front Neuroanat 9:5. https://doi.org/10.3389/fnana.2015.00005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Little S, Pogosyan A, Kuhn AA, Brown P (2012) Beta band stability over time correlates with Parkinsonian rigidity and bradykinesia. Exp Neurol 236:383–388. https://doi.org/10.1016/j.expneurol.2012.04.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Beck MH, Haumesser JK, Kuhn J, Altschuler J, Kuhn AA, van Riesen C (2016) Short- and long-term dopamine depletion causes enhanced beta oscillations in the cortico-basal ganglia loop of parkinsonian rats. Exp Neurol 286:124–136. https://doi.org/10.1016/j.expneurol.2016.10.005

    Article  CAS  PubMed  Google Scholar 

  11. Boix J, Padel T, Paul G (2015) A partial lesion model of Parkinson’s disease in mice – characterization of a 6-OHDA-induced medial forebrain bundle lesion. Behav Brain Res 284:196–206. https://doi.org/10.1016/j.bbr.2015.01.053

    Article  CAS  PubMed  Google Scholar 

  12. Olsson M, Nikkhah G, Bentlage C, Bjorklund A (1995) Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. J Neurosci 15:3863–3875. https://www.ncbi.nlm.nih.gov/pubmed/7751951

  13. Caputi V, Giron MC (2018) Microbiome-gut-brain axis and toll-like receptors in Parkinson’s disease. Int J Mol Sci 19(16):1689. https://doi.org/10.3390/ijms19061689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Houser MC, Tansey MG (2017) The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis 3:3. https://doi.org/10.1038/s41531-016-0002-0

    Article  PubMed  PubMed Central  Google Scholar 

  15. Liu WH, Chuang HL, Huang YT, Wu CC, Chou GT, Wang S, Tsai YC (2016) Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice. Behav Brain Res 298:202–209. https://doi.org/10.1016/j.bbr.2015.10.046

    Article  CAS  PubMed  Google Scholar 

  16. Liu YW, Liu WH, Wu CC, Juan YC, Wu YC, Tsai HP, Wang S, Tsai YC (2016) Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naive adult mice. Brain Res 1631:1–12. https://doi.org/10.1016/j.brainres.2015.11.018

    Article  CAS  PubMed  Google Scholar 

  17. Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74:720–726. https://doi.org/10.1016/j.biopsych.2013.05.001

    Article  CAS  PubMed  Google Scholar 

  18. Huang WC, Wei CC, Huang CC, Chen WL, Huang HY (2019) The beneficial effects of Lactobacillus plantarum PS128 on high-intensity, exercise-induced oxidative stress, inflammation, and performance in triathletes. Nutrients 11(2):353. https://doi.org/10.3390/nu11020353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Liao JF, Cheng YF, You ST, Kuo WC, Huang CW, Chiou JJ, Hsu CC, Hsieh-Li HM, Wang S, Tsai YC (2020) Lactobacillus plantarum PS128 alleviates neurodegenerative progression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse models of Parkinson’s disease. Brain Behav Immun. https://doi.org/10.1016/j.bbi.2020.07.036

    Article  PubMed  Google Scholar 

  20. Liao PL, Wu CC, Chen TY, Tsai YC, Peng WS, Yang DJ, Kang JJ (2019) Toxicity studies of Lactobacillus plantarum PS128(TM) isolated from spontaneously fermented mustard greens. Foods 8(12):668. https://doi.org/10.3390/foods8120668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Deumens R, Blokland A, Prickaerts J (2002) Modeling Parkinson’s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 175:303–317. https://doi.org/10.1006/exnr.2002.7891

    Article  CAS  PubMed  Google Scholar 

  22. Perese DA, Ulman J, Viola J, Ewing SE, Bankiewicz KS (1989) A 6-hydroxydopamine-induced selective parkinsonian rat model. Brain Res 494:285–293. https://www.ncbi.nlm.nih.gov/pubmed/2528389

  23. Chuang CF, Wu CW, Weng Y, Hu PS, Yeh SR, Chang YC (2018) High-frequency stimulation of the subthalamic nucleus activates motor cortex pyramidal tract neurons by a process involving local glutamate, GABA and dopamine receptors in hemi-Parkinsonian rats. Chin J Physiol 61:92–105. https://doi.org/10.4077/CJP.2018.BAG561

    Article  CAS  PubMed  Google Scholar 

  24. Grealish S, Mattsson B, Draxler P, Bjorklund A (2010) Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson’s disease. Eur J Neurosci 31:2266–2278. https://doi.org/10.1111/j.1460-9568.2010.07265.x

    Article  PubMed  Google Scholar 

  25. Liao JF, Cheng YF, Li SW, Lee WT, Hsu CC, Wu CC, Jeng OJ, Wang S, Tsai YC (2019) Lactobacillus plantarum PS128 ameliorates 2,5-dimethoxy-4-iodoamphetamine-induced tic-like behaviors via its influences on the microbiota-gut-brain-axis. Brain Res Bull 153:59–73. https://doi.org/10.1016/j.brainresbull.2019.07.027

    Article  CAS  PubMed  Google Scholar 

  26. Cenci MA (2014) Presynaptic mechanisms of l-DOPA-induced dyskinesia: the findings, the debate, and the therapeutic implications. Front Neurol 5:242. https://doi.org/10.3389/fneur.2014.00242

    Article  PubMed  PubMed Central  Google Scholar 

  27. Su RJ, Zhen JL, Wang W, Zhang JL, Zheng Y, Wang XM (2018) Time-course behavioral features are correlated with Parkinson’s disease-associated pathology in a 6-hydroxydopamine hemiparkinsonian rat model. Mol Med Rep 17:3356–3363. https://doi.org/10.3892/mmr.2017.8277

    Article  CAS  PubMed  Google Scholar 

  28. Blume SR, Cass DK, Tseng KY (2009) Stepping test in mice: a reliable approach in determining forelimb akinesia in MPTP-induced Parkinsonism. Exp Neurol 219:208–211. https://doi.org/10.1016/j.expneurol.2009.05.017

    Article  PubMed  Google Scholar 

  29. Tropea TF, Chen-Plotkin AS (2018) Unlocking the mystery of biomarkers: a brief introduction, challenges and opportunities in Parkinson Disease. Parkinsonism Relat Disord 46(Suppl 1):S15–S18. https://doi.org/10.1016/j.parkreldis.2017.07.021

    Article  PubMed  Google Scholar 

  30. Beudel M, Oswal A, Jha A, Foltynie T, Zrinzo L, Hariz M, Limousin P, Litvak V (2017) Oscillatory beta power correlates with akinesia-rigidity in the Parkinsonian subthalamic nucleus. Mov Disord 32:174–175. https://doi.org/10.1002/mds.26860

    Article  PubMed  Google Scholar 

  31. Swan CB, Schulte DJ, Brocker DT, Grill WM (2019) Beta frequency oscillations in the subthalamic nucleus are not sufficient for the development of symptoms of Parkinsonian bradykinesia/akinesia in rats. eNeuro 6. https://doi.org/10.1523/ENEURO.0089-19.2019

  32. Dupre KB, Cruz AV, McCoy AJ, Delaville C, Gerber CM, Eyring KW, Walters JR (2016) Effects of L-dopa priming on cortical high beta and high gamma oscillatory activity in a rodent model of Parkinson’s disease. Neurobiol Dis 86:1–15. https://doi.org/10.1016/j.nbd.2015.11.009

    Article  CAS  PubMed  Google Scholar 

  33. Gaetz W, Edgar JC, Wang DJ, Roberts TP (2011) Relating MEG measured motor cortical oscillations to resting gamma-aminobutyric acid (GABA) concentration. Neuroimage 55:616–621. https://doi.org/10.1016/j.neuroimage.2010.12.077

    Article  CAS  PubMed  Google Scholar 

  34. Fiber JM, Etgen AM (2001) Modulation of GABA-augmented norepinephrine release in female rat brain slices by opioids and adenosine. Neurochem Res 26:853–858. https://doi.org/10.1023/a:1011676505575

    Article  CAS  PubMed  Google Scholar 

  35. Meiser J, Weindl D, Hiller K (2013) Complexity of dopamine metabolism. Cell Commun Signal 11:34. https://doi.org/10.1186/1478-811X-11-34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Arima Y, Harada M, Kamimura D, Park JH, Kawano F, Yull FE, Kawamoto T, Iwakura Y, Betz UA, Marquez G et al (2012) Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier. Cell 148:447–457. https://doi.org/10.1016/j.cell.2012.01.022

    Article  CAS  PubMed  Google Scholar 

  37. Duty S, Jenner P (2011) Animal models of Parkinson’s disease: a source of novel treatments and clues to the cause of the disease. Br J Pharmacol 164:1357–1391. https://doi.org/10.1111/j.1476-5381.2011.01426.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liu YW, Liong MT, Chung YE, Huang HY, Peng WS, Cheng YF, Lin YS, Wu YY, Tsai YC (2019) Effects of Lactobacillus plantarum PS128 on children with autism spectrum disorder in Taiwan: a randomized, double-blind, placebo-controlled trial. Nutrients 11(4):820. https://doi.org/10.3390/nu11040820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Bened Biomedical Co., Ltd. for providing PS128 used in this study. We also appreciate EzInstrument Technology Co., Ltd. for providing electrophysiology instruments and technical support.

Funding

This work was supported by Bened Biomedical Co., Ltd. The funding source had no contribution to the study design, analysis, interpretation of the data, or writing of the report for publication.

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Contributions

Conceptualization, SRY and YCT; data curation, YFM and YAL; formal analysis, YFM, SW and YAL; investigation, YFM and YAL; methodology, YFM, YAL, CLH, SW, and SRY; project administration, YFM and CCH; resources, CCH, SRY, and YCT; supervision, SRY and YCT; writing — original draft, YFM; writing — review and editing, YFM, SW, SRY, and YCT. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Sabrina Wang, Shih-Rung Yeh or Ying-Chieh Tsai.

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Conflict of Interest

CLH and CCH were employed by Bened Biomedical Co., Ltd. at the time of the study. YCT owns stock of Bened Biomedical Co., Ltd. None of the other authors had a personal or financial conflict of interest.

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Ma, YF., Lin, YA., Huang, CL. et al. Lactiplantibacillus plantarum PS128 Alleviates Exaggerated Cortical Beta Oscillations and Motor Deficits in the 6-Hydroxydopamine Rat Model of Parkinson’s Disease. Probiotics & Antimicro. Prot. 15, 312–325 (2023). https://doi.org/10.1007/s12602-021-09828-x

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