Effects of Native Iranian Probiotic Mix on Serum TNF-α Levels and Anxiety-like Behavior in 6-OHDA-Induced Parkinsonian Rats

Document Type : Research Article

Authors

1 Department of Genetics, TeMS.C. Islamic Azad University, Tehran, Iran

2 Department of Biology, Faculty of Sciences, Islamic Azad University, Tehran, Iran

10.22080/jgr.2026.30903.1453

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and the presence of both motor and non-motor symptoms. Recent studies suggest that the gut–brain axis and probiotics play important roles in modulating neuroinflammation and behavioral alterations in PD. This study aimed to investigate the effects of an indigenous Iranian probiotic mixture on anxiety-like behaviors and serum TNF-α levels in a 6-hydroxydopamine (6-OHDA) rat model of Parkinson’s disease. Fifteen adult male Wistar rats were randomly divided into three groups: control, 6-OHDA + saline, and 6-OHDA + probiotics. Parkinsonism was induced by stereotaxic injection of 6-OHDA (10 µg in 2 µL saline with 0.02% ascorbic acid) into the right striatum. The probiotic mixture (~10⁹ CFU/mL; 1 mL/day) was administered orally for 21 days. Behavioral tests, including apomorphine-induced rotation, elevated plus maze, forced swim test, and cylinder test, were performed. Serum TNF-α levels were measured using ELISA. Probiotic supplementation significantly reduced motor asymmetry and improved anxiety- and depressive-like behaviors compared with the Parkinsonian group (p< 0.01). Serum TNF-α concentrations also decreased markedly in the probiotic-treated rats, indicating anti-inflammatory effects. Indigenous Iranian probiotics exhibited neuroprotective and anti-inflammatory properties in the PD model, suggesting their potential as safe, complementary treatments for managing both motor and non-motor symptoms of Parkinson’s disease. The use of a combination of indigenous Iranian probiotic strains, each possessing unique biological properties, may represent an advantage over previous studies that investigated only one or a limited number of probiotic species.

Keywords

Main Subjects

References

Bloem, B. R., Okun, M. S., & Klein, C. (2021). Parkinson’s disease. The Lancet, 397(10291), 2284-2303. http://doi.org/10.1016/S0140-6736(21)00218-X
Blesa, J., Trigo-Damas, I., Dileone, M., del Rey, N. L. G., Hernández, L. F., & Obeso, J. A. (2022). Oxidative stress and Parkinson’s disease. Frontiers in Aging Neuroscience, 14, 833221. http://doi.org/10.3389/fnana.2015.00091
Boka, G., Anglade, P., Wallach, D., Javoy-Agid, F., Agid, Y., & Hirsch, E. C. (1994). Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s disease. Neuroscience Letters, 172(1-2), 151-154. http://doi.org/10.1016/0304-3940(94)90684-X
Bradley, J. R. (2008). TNF-mediated inflammatory disease. The Journal of Pathology, 214(2), 149-160. https://doi.org/10.1002/path.2287
Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., … & Cryan, J. F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050-16055. https://doi.org/10.1073/pnas.1102999108
Carobrez, A. P., & Bertoglio, L. J. (2005). Ethological and temporal analyses of anxiety-like behavior: the elevated plus-maze model 20 years on. Neuroscience and Biobehavioral Reviews, 29(8),1193-1205. https://doi.org/10.1016/j.neubiorev.2005.04.017
Chang, P. V., Hao, L., Offermanns, S., & Medzhitov, R. (2014). The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proceedings of the National Academy of Sciences, 111(6), 2247-2252. https://doi.org/10.1073/pnas.1322269111
Connolly, B. S., & Lang, A. E. (2014). Pharmacological treatment of Parkinson disease: a review. Journal of the American Medical Association, 311(16), 1670-1683. https://doi.org/10.1001/jama.2014.3654
Cryan, J. F., O’Riordan, K. J., Cowan, C. S., Sandhu, K. V., Bastiaanssen, T. F., Boehme, M., … & Dinan, T. G. (2019). The microbiota-gut-brain axis. Physiological Reviews, 99(4), 1877-2019. https://doi.org/10.1152/physrev.00018.2018
Ferger, B., Leng, A., Mura, A., Hengerer, B., & Feldon, J. (2004). Genetic ablation of TNF-α does not protect against 6-OHDA-induced dopaminergic neurodegeneration. Experimental Neurology, 187(2), 286-292. https://doi.org/10.1111/j.14714159.2004.02399.x
Foster, J. A., Rinaman, L., & Cryan, J. F. (2017). Stress & the gut–brain axis: Regulation by the microbiome. Neurobiology of Stress, 7, 124-136. https://doi.org/10.1016/j.ynstr.2017.03.001
Furrie, E., Macfarlane, S., Kennedy, A., Cummings, J. H., Walsh, S. V., O’neil, D. A., & Macfarlane, G. T. (2005). Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut, 54(2), 242-249.‏ https://doi.org/10.1136/gut.2004.044834
Heydari, A., Parvini, F., & Allahyari Fard, N. (2025). Transcriptomic analysis of probiotic oxidative stress resistance in anti-inflammatory pathways. Journal of Genetic Resources, 11(2), 146-159.‏ https://doi.org/10.22080/jgr.2025.28783.1428
Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., ... & Sanders, M. E. (2014). Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews. Gastroenterology and Hepatology, 11(8), 506-514.‏ https://doi.org/10.1038/nrgastro.2014.66
Kalia, L. V., & Lang, A. E. (2015). Parkinson's disease. The Lancet, 386(9996), 896-912.‏ https://doi.org/10.1016/S0140-6736(14)61393-3
Khalesi, S., Sun, J., Buys, N., & Jayasinghe, R. (2014). Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials. Hypertension, 64(4), 897-903.‏ https://doi.org/10.1161/HYPERTENSIONAHA.114.03469
Magistrelli, L., Contaldi, E., Visciglia, A., Deusebio, G., Pane, M., & Amoruso, A. (2024). The impact of probiotics on clinical symptoms and peripheral cytokines levels in Parkinson’s disease: preliminary in vivo data. Brain Sciences, 14(11), 1147.‏ https://doi.org/10.3390/brainsci14111147
McCoy, M. K., & Tansey, M. G. (2008). TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. Journal of Neuroinflammation, 5(1), 45.‏ https://doi.org/10.1186/1742-2094-5-45
Mulak, A., & Bonaz, B. (2015). Brain-gut-microbiota axis in Parkinson’s disease. World Journal of Gastroenterology, 21(37), 10609-10620. https://doi.org/10.3748/wjg.v21.i37.10609
Garber, J. C., Barbee, R. W., Bielitzki, J. T., Clayton, L. A., Donovan, J. C., Hendriksen, C., … National Research Council. (2011). Guide for the care and use of laboratory animals (8th eds.). National Academy of Sciences, USA.
Ouwehand, A. C., Salminen, S., & Isolauri, E. (2002). Probiotics: An overview of beneficial effects. Antonie van Leeuwenhoek, 82(1), 279-289. https://doi.org/10.1023/A:1020620607611
Paxinos, G., & Watson, C. (2006). The rat brain in stereotaxic coordinates (6th eds.). Academic Press.
Pont-Sunyer, C., Hotter, A., Gaig, C., Seppi, K., Compta, Y., Katzenschlager, R., … & Tolosa, E. (2015). The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Movement Disorders, 30(2), 229-237. https://doi.org/10.1002/mds.26077
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., ... & Mazmanian, S. K. (2016). Gut microbiota regulates motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell, 167(6), 1469-1480. https://doi.org/10.1016/j.cell.2016.11.018
Savignac, H. M., Corona, G., Mills, H., Chen, L., Spencer, J. P., Tzortzis, G., & Burnet, P. W. (2013). Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochemistry International, 63(8), 756-764.‏ https://doi.org/10.1016/j.neuint.2013.10.006
Schapira, A. H., Chaudhuri, K. R., & Jenner, P. (2017). Non-motor features of Parkinson disease. Nature Reviews Neuroscience, 18(7), 435-450. https://doi.org/10.1038/nrn.2017.62
Sun, M. F., Zhu, Y. L., Zhou, Z. L., Jia, X. B., Xu, Y. D., Yang, Q., … & Zhu, J. (2018). Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson’s disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway. Brain, Behavior, and Immunity, 70, 48-60. https://doi.org/10.1016/j.bbi.2018.02.005
Ungerstedt, U. (1971). Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiologica Scandinavica, 82(S367), 49-68.‏ https://doi.org/10.1111/j.1365201X.1971.tb109x
Wang, H., Lee, I. S., Braun, C., & Enck, P. (2016). Effect of probiotics on central nervous system functions in animals and humans: A systematic review. Journal of Neurogastroenterology and Motility, 22(4), 171-182. https://doi.org/10.5056/jnm16018
Journal of Genetic Resources
Volume 12, Issue 1
Issue in Progress
2026
Pages 11-19

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