فلاونوئید مورین رفتارهای اضطرابی و افسردگی القاشده توسط پپتید آمیلوئید بتا را در موش‌های صحرایی کاهش می‌دهد

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه فیزیولوژی، واحد زنجان، دانشگاه آزاد اسلامی، زنجان، ایران

2 گروه زیست‌شناسی، واحد زنجان، دانشگاه آزاد اسلامی، زنجان، ایران

چکیده

مقدمه و هدف: مطالعات نشان داده است که قبل از بروز نقص حافظه در بیماری آلزایمر، اضطراب و افسردگی ظاهر می‌شود و مهار این اختلالات، احتمالاً از پیدایش و پیشرفت اختلال حافظه جلوگیری می‌کند. مورین نوعی فلاونول طبیعی است که دارای اثرات آنتی اکسیدانی، ضدالتهابی و محافظت کنندگی عصبی است. در این مطالعه، اثر مورین بر رفتارهای اضطرابی و افسردگی القاشده توسط پپتید آمیلوئید بتا در موش‌های بزرگ آزمایشگاهی بررسی شد.
مواد و روش ها: 40 سر موش بزرگ آزمایشگاهی نر نژاد ویستار به گروه‌های کنترل، مورین، آمیلوئید بتا و آمیلوئید بتا-مورین تقسیم شدند. آمیلوئید بتا 42-1 به صورت درون هیپوکامپی (هر طرف 4 میکروگرم) تزریق شد و مورین (20 mg/kg) نیز به صورت گاواژ به مدت 14 روز متوالی تیمار شد. در پایان دوره به ترتیب از ماز بعلاوه مرتفع و تست شنای اجباری برای بررسی رفتارهای اضطرابی و افسردگی استفاده شد.
نتایج: تزریق درون هیپوکامپی آمیلوئید بتا موجب کاهش معنی‌‌دار درصد ورود به بازوی باز و درصد زمان ماندن در بازوی باز در ماز بعلاوه مرتفع شد (001/0>P). مجموع زمان بی‌حرکتی این حیوانات نیز در تست شنای اجباری به طور چشمگیری افزایش یافت (001/0>P). مورین تا حد زیادی از بروز این تغییرات در موش‌های بزرگ آزمایشگاهی دریافت کننده آمیلوئید بتا ممانعت نمود.
نتیجه‌گیری: مورین از بروز رفتارهای اضطرابی و افسردگی در موش های بزرگ مدل بیماری آلزایمر جلوگیری می‌کند و احتمالاً اثرات محافظت کنندگی عصبی در برابر آمیلوئید بتا دارد.

کلیدواژه‌ها


عنوان مقاله [English]

The effect of flavonoid morin on anxiety and depression behaviors induced by amyloid-beta peptide in rats

نویسندگان [English]

  • Negin Mohammadi 1
  • Masoumeh Asle-Rousta 1
  • Mehdi Rahnema 1
  • Rahim Amini 2
1 Department of Physiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran
2 Department of Biology, Zanjan Branch, Islamic Azad University, Zanjan, Iran
چکیده [English]

Background and Objective: Studies have shown that anxiety and depression appear before memory impairment in Alzheimer's disease and controlling these dysfunctions may prevent the onset and progression of memory deficit. Morin is a natural flavonol that has antioxidant, anti-inflammatory, and neuroprotective effects. In this study, we investigated the effect of morin on anxiety and depression behaviors induced by amyloid-beta peptide in rats.
Materials and Methods: Forty male Wistar rats were divided into control, morin, amyloid-beta, and amyloid-beta-morin groups. Amyloid-beta 1-42 was injected into the hippocampus (4 micrograms on each side) and morin (20 mg/kg) was treated by gavage for 14 consecutive days. At the end of the period,  elevated plus maze (EPM) and forced swimming tests were used to evaluate anxiety and depressive behaviors, respectively.
Results: Intrahippocampal injection of amyloid-beta significantly reduced the percentage of entry into the open arm and the percentage of time remaining in the open arm in the EPM (P < 0.001). Also, the total immobility time of these animals in the forced swimming test was significantly increased (P < 0.001). Morin largely prevented these changes in amyloid-beta injected rats.
Conclusion: Morin prevents anxiety behaviors and depression in Alzheimer's disease model rats and may have neuroprotective effects against amyloid-beta.

کلیدواژه‌ها [English]

  • Morin
  • Anxiety
  • Depression
  1. Abeysinghe AA, Deshapriya RD, Udawatte C. Alzheimer's disease; a review of the pathophysiological basis and therapeutic interventions. Life Sciences 2020;256:117996. doi: 10.1016/j.lfs.2020.117996.
  2. Chen Z, Zhong C. Oxidative stress in Alzheimer’s disease. Neuroscience Bulletin 2014;30(2):271-81. doi: 10.1007/s12264-013-1423-y.
  3. Sinyor B, Mineo J, Ochner C. Alzheimer’s Disease, Inflammation, and the Role of Antioxidants. Journal of Alzheimer's Disease Reports 2020;4:175-83. doi: 10.3233/ADR-200171.
  4. Salim S, Asghar M, Taneja M, Hovatta I, Chugh G, Vollert C, et al. Potential contribution of oxidative stress and inflammation to anxiety and hypertension. Brain Research 2011;1404:63-71. doi: 10.1016/j.brainres.2011.06.024.
  5. Rawdin BJ, Mellon SH, Dhabhar FS, Epel ES, Puterman E, Su Y, et al. Dysregulated relationship of inflammation and oxidative stress in major depression. Brain, Behavior, and Immunity 2013;31:143-52. doi: 10.1016/j.bbi.2012.11.011.
  6. Pietrzak RH, Lim YY, Neumeister A, Ames D, Ellis KA, Harrington K, et al. Amyloid-β, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study. JAMA Psychiatry 2015;72(3):284-91. doi: 10.1001/jamapsychiatry.2014.2476.
  7. Donovan NJ, Locascio JJ, Marshall GA, Gatchel J, Hanseeuw BJ, Rentz DM, et al. Harvard Aging Brain Study. Longitudinal association of amyloid beta and anxious-depressive symptoms in cognitively normal older adults. American Journal of Psychiatry 2018;175:530-7. doi: 10.1176/appi.ajp.2017.17040442.
  8. Kim JK, Park SU. Flavonoids for treatment of Alzheimer's disease: An up to date review. EXCLI Journal 2021;20:495-502. doi: 10.17179/excli2021-3492.
  9. Caselli A, Cirri P, Santi A, Paoli P. Morin: a promising natural drug. Current Medicinal Chemistry 2016;23(8):774-91. doi: 10.2174/0929867323666160106150821.
  10. Lee HS, Jung KH, Hong SW, Park IS, Lee C, Han HK, et al. Morin protects acute liver damage by carbon tetrachloride (CCl 4) in rat. Archives of Pharmacal Research 2008;31(9):1160-5. doi: 10.1007/s12272-001-1283-5.
  11. Subash S, Subramanian P. Morin a flavonoid exerts antioxidant potential in chronic hyperammonemic rats: a biochemical and histopathological study. Molecular and Cellular Biochemistry 2009;327(1):153-61. doi: 10.1007/s11010-009-0053-1.
  12. Kapoor R, Kakkar P. Protective role of morin, a flavonoid, against high glucose induced oxidative stress mediated apoptosis in primary rat hepatocytes. PLoS One 2012;7(8):e41663. doi: 10.1371/journal.pone.0041663.
  13. Ola MS, Aleisa AM, Al-Rejaie SS, Abuohashish HM, Parmar MY, Alhomida AS, et al. Flavonoid, morin inhibits oxidative stress, inflammation and enhances neurotrophic support in the brain of streptozotocin-induced diabetic rats. Neurological Sciences 2014;35(7):1003-8. doi: 10.1007/s10072-014-1628-5.
  14. Lee KM, Lee Y, Chun HJ, Kim AH, Kim JY, Lee JY, et al. Neuroprotective and anti-inflammatory effects of morin in a murine model of Parkinson's disease. Journal of Neuroscience Research 2016;94(10):865-78. doi: 10.1002/jnr.23764.
  15. Gong EJ, Park HR, Kim ME, Piao S, Lee E, Jo DG, et al. Morin attenuates tau hyperphosphorylation by inhibiting GSK3β. Neurobiology of Disease 2011;44(2):223-30. doi: 10.1016/j.nbd.2011.07.005.
  16. Alberdi E, Sánchez-Gómez MV, Ruiz A, Cavaliere F, Ortiz-Sanz C, Quintela-Lopez T, et al. Mangiferin and morin attenuate oxidative stress, mitochondrial dysfunction, and neurocytotoxicity, induced by amyloid beta oligomers. Oxidative Medicine and Cellular Longevity 2018;2018:2856063. doi: 10.1155/2018/2856063.
  17. Liu H, Li S, Yang C, Jia H, Gu Z, Tu X, et al. D-serine Ameliorates Motor and Cognitive Impairments in β-amyloid 1-42 Injected Mice by Inhibiting JNK Signaling Pathway. Journal of Chemical Neuroanatomy 2020;109:101852. doi: 10.1016/j.jchemneu.2020.101852.
  18. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. New York: Academic Press 2006.
  19. Fadaei S, Asle-Rousta M. Anxiolytic and antidepressant effects of cinnamon (Cinnamomum verum) extract in rats receiving lead acetate. Scientific Journal of Kurdistan University of Medical Sciences 2018, 22(6): 31-39.
  20. Maghsoud-Nia L, Asle-Rousta M, Rahnema M, Amini R. Sesame Oil and Its Component Oleic Acid Ameliorate Behavioral and Biochemical Alterations in Socially Isolated Rats. Iranian Journal of Science and Technology, Transactions A: Science 2021:1-9. doi: 10.1007/s40995-021-01098-0.
  21. Cioanca O, Hritcu L, Mihasan M, Trifan A, Hancianu M. Inhalation of coriander volatile oil increased anxiolytic–antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1–42) rat model of Alzheimer's disease. Physiology & Behavior 2014;131:68-74. doi: 10.1016/j.physbeh.2014.04.021.
  22. Song X, Liu B, Cui L, Zhou B, Liu W, Xu F, et al. Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus. Physiology & Behavior 2017;179:487-93. doi: 10.1016/j.physbeh.2017.07.023.
  23. Olonode ET, Aderibigbe AO, Adeoluwa OA, Eduviere AT, Ben-Azu B. Morin hydrate mitigates rapid eye movement sleep deprivation-induced neurobehavioural impairments and loss of viable neurons in the hippocampus of mice. Behavioural Brain Research 2019;356:518-25. doi: 10.1016/j.bbr.2017.12.024.
  24. Olonode ET, Aderibigbe AO, Adeoluwa OA, Ajayi AM. Protective effects of morin hydrate on acute stress-induced behavioral and biochemical alterations in mice.  Basic and Clinical Neuroscience 2018;9(3):195-208. doi: 10.29252/NIRP.BCN.9.3.195.
  25. Ben-Azu B, Aderibigbe AO, Ajayi AM, Eneni AE, Umukoro S, Iwalewa EO. Involvement of GABAergic, BDNF and Nox-2 mechanisms in the prevention and reversal of ketamine-induced schizophrenia-like behavior by morin in mice. Brain Research Bulletin 2018;139:292-306. doi: 10.1016/j.brainresbull.2018.03.006.
  26. Sanders SK, Shekhar A. Regulation of anxiety by GABAA receptors in the rat amygdala. Pharmacology Biochemistry and Behavior 1995;52(4):701-6. doi: 10.1016/0091-3057(95)00153-N.
  27. Hassan MA, Gad AM, Menze ET, Badary OA, El-Naga RN. Protective effects of morin against depressive-like behavior prompted by chronic unpredictable mild stress in rats: Possible role of inflammasome-related pathways. Biochemical Pharmacology 2020;180:114140. doi: 10.1016/j.bcp.2020.114140.
  28. Karolewicz B, Maciag D, O'Dwyer G, Stockmeier CA, Feyissa AM, Rajkowska G. Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression. International Journal of Neuropsychopharmacology 2010;13(4):411-20. doi: 10.1017/S1461145709990587.
  29. Çelik H, Kucukler S, Çomaklı S, Özdemir S, Caglayan C, Yardım A, et al. Morin attenuates ifosfamide-induced neurotoxicity in rats via suppression of oxidative stress, neuroinflammation and neuronal apoptosis. Neurotoxicology 2020;76:126-37. doi: 10.1016/j.neuro.2019.11.004.
  30. Lucassen PJ, Müller MB, Holsboer F, Bauer J, Holtrop A, Wouda J, et al. Hippocampal apoptosis in major depression is a minor event and absent from subareas at risk for glucocorticoid overexposure. The American Journal of Pathology 2001;158(2):453-68. doi: 10.1016/S0002-9440(10)63988-0.
  31. Ko YH, Kim SK, Lee SY, Jang CG. Flavonoids as therapeutic candidates for emotional disorders such as anxiety and depression. Archives of Pharmacal Research 2020;22:1-6. doi: 10.1007/s12272-020-01292-5.