The Effect of Betaine on Cerebellar Histological Alterations, Balance, Motor Function on Male Rats, an Experimental Model of Multiple Sclerosis

Document Type : Original Article (s)

Authors

1 PhD Candidate of Comparative Histology, Division of Basic Sciences, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Assistant Professor, Department of Basic Sciences, Division of Histology, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Associate Professor, Department of Basic Sciences, Division of Biochemistry and Molecular Biology, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

4 Associate Professor, Department of Basic Sciences, Division of Physiology, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

5 Assistant Professor, Department of Basic Sciences, Division of Anatomy and Embryology, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Background: One of the chronic inflammatory diseases of the central nervous system is multiple sclerosis (MS). Betaine has anti-inflammatory and neuroprotective effects. The present study was conducted with the aim of investigating the effect of betaine on tissue changes of the cerebellum and motor activity in the experimental model of MS.
Methods: In this experimental research, 20 adult male rats (12-week-old) were divided into control, Ms, Ms+ betaine and betaine. To create the MS model, animals were fed food containing 0.5% cuprizone for 12 weeks. For treatment, betaine was given at a dose of 1% in drinking water for the last 6 weeks. At the end of period, in order to measure balance and motor coordination, rotarod, open field, and inverted grid tests were performed, and the cerebellum of the animals was studied in terms of histological alterations.
Findings: Motor activities and maintaining balance in the MS group showed a significant decrease compared to control group, while treatment with betaine improved these symptoms. In the histological studies, tissue changes in Purkinje cells, such as a decrease in the number, condensation and pyknosis of the nucleus, a decrease in the diameter of the cell body and the nucleus of these cells were seen in the MS group. While the MS group receiving betaine, the changes were clearly improved and the Purkinje cells were able to maintain their number and shape.
Conclusion: The betaine can be considered as an effective biomolecule in the process of nerve regeneration and improvement of motor behaviors in patients with MS.

Keywords

Main Subjects


  1. Khezri S, Samadi S, Rahmani F, Tarbali S. Molecular study of the effect of progesterone on optic chiasm in male rat following ethidium bromide-induced demyelination [in Persian]. J Mazandaran Univ Med Sci 2016; 25(133): 206-17.
  2. López-Muguruza E, Matute C. Alterations of oligodendrocyte and myelin energy metabolism in multiple sclerosis. Int J Mol Sci 2023; 24(16): 12912.
  3. Shirazi A, Golab F, Sanadgol N, Barati M, Mohammad Salehi R, Vahabzadeh G, et al. Evaluation of the neurotrophic factors in animal model of myelin destruction induced by cuprizone in c57bl/6 mice [in Persian]. Shefaye Khatam 2016; 4(2): 47-54.
  4. Ghaiad HR, Abd-Elmawla MA, Gad ES, Ahmed KA,
    Abdelmonem M. Modulating miR-146a expression by hydrogen sulfide ameliorates motor dysfunction and axonal demyelination in cuprizone-induced multiple sclerosis. ACS Chem Neurosci 2023; 14(17):3047-58.
  5. Chasiotis AK, Kitsos DK, Stavrogianni K, Giannopapas V, Papadopoulou M, Zompola C, et al. Rehabilitation on cerebellar ataxic patients with multiple sclerosis: A systematic review. J Neurosci Res 2023; 101(12):1773-80.
  6. Sternbach S, McDonough J. Betaine as a neuroprotective therapy in multiple sclerosis. Treatments, Nutraceuticals, Supplements, and Herbal Medicine in Neurological Disorders: Elsevier; 2023. p. 443-52.
  7. Rahmani B, Zendehdel M, Babapour V, Sadeghinezhad J, Alirezaei M. Evaluation of betaine neuroprotective effects on 6-hydroxy dopamine induced hemi parkinsonism in male wistar rats. Iranian Journal of Veterinary Medicine 2019; 13(3): 290-302.
  8. Zhang W, Xiong BR, Zhang LQ, Huang X, Yuan X, Tian YK, et al. The role of the GABAergic system in diseases of the central nervous system. Neuroscience 2021; 470: 88-99.
  9. Zimmermann J, Emrich M, Krauthausen M, Saxe S, Nitsch L, Heneka MT, et al. IL-17A promotes granulocyte infiltration, myelin loss, microglia activation, and behavioral deficits during cuprizone-induced demyelination. Mol Neurobiol 2018; 55(2): 946-57.
  10. Singhal NK, Sternbach S, Fleming S, Alkhayer K, Shelestak J, Popescu D, et al. Betaine restores epigenetic control and supports neuronal mitochondria in the cuprizone mouse model of multiple sclerosis. Epigenetics 2020; 15(8): 871-86.
  11. Ghotbeddin Z, Basir Z, Jamshidian J, Delfi F. Modulation of behavioral responses and CA1 neuronal death by nitric oxide in the neonatal rat's hypoxia model. Brain Behav 2020; 10(11): e01841.
  12. Ghotbeddin Z, Khazaeel K, Tabandeh MR, Aliheydari M, Yaghoubi H. Effects of omega-3 fatty acid supplementation during chronic maternal hypoxia on behavioral disorders in male rat offspring: The role of Trk family and oxidative stress. Metabolic Brain Disease 2022; 37(6): 1959-67.
  13. Jansone B, Dzirkale Z, Jekabsons K, Pilipenko V, Beitnere U, Māgure I, et al. editors. Spruce needle polyprenols protect against atorvastatin-induced muscle weakness and do not influence central nervous system functions in rats. Proceedings of the Latvian Academy of Sciences Section B Natural, Exact, and Applied Sciences 2016; 70(1): 1320.
  14. Omotoso GO, Gbadamosi IT, Afolabi TT, Abdulwahab AB, Akinlolu AA. Ameliorative effects of Moringa on cuprizone-induced memory decline in rat model of multiple sclerosis. Anat Cell Biol 2018; 51(2): 119-27.
  15. Beckmann DV, Carvalho FB, Mazzanti CM, Dos Santos RP, Andrades AO, Aiello G, et al. Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide. Life Sci 2014; 103(2): 79-87.
  16. Omotoso GO, Arietarhire LO, Ukwubile II, Gbadamosi IT. The protective effect of kolaviron on molecular, cellular, and behavioral characterization of cerebellum in the rat model of demyelinating diseases. Basic Clin Neurosci 2020; 11(5): 609-18.
  17. Hashemi R, Morshedi M, Jafarabadi MA, Altafi D, Hosseini-Asl SS, Rafie-Arefhosseini S. Anti-inflammatory effects of dietary vitamin D3 in patients with multiple sclerosis. Neurology genetics 2018; 4(6): e278.
  18. Ünsal C, Özcan M. Neurotoxicity of cuprizone in female and male rats: Electrophysiological observations. Neurophysiology 2018; 50: 108-15.
  19. Li Q, Qu M, Wang N, Wang L, Fan G, Yang C. Betaine protects rats against ischemia/reperfusion injury-induced brain damage. J Neurophysiol 2022; 127(2): 444-51.
  20. Redondo J, Kemp K, Hares K, Rice C, Scolding N, Wilkins A. Purkinje cell pathology and loss in multiple sclerosis cerebellum. Brain Pathol 2015; 25(6): 692-700.
  21. Eslami M, Alizade L, Sayyah M. The effect of lipopolysaccharide pretreatment on trauma-induced dark neurons in the hippocampus [in Persian]. Shefaye Khatam 2018; 6(1): 41-8.
  22. Alipourfard F, Shajiee H, Nazari-Serenjeh F, Hojati V, Alirezaie M. Betaine attenuates oxidative stress and cognitive dysfunction in an amyloid β-induced rat model of Alzheimer’s disease. Res Pharm Sci 2023; 18(3): 270-8.
Volume 41, Issue 734
2nd Week, November
November and December 2023
Pages 773-779
  • Receive Date: 16 July 2023
  • Revise Date: 20 September 2023
  • Accept Date: 20 September 2023