بررسی اثر تجویز کروسین بر اختلالات حافظه شناختی و مرگ سلولی در ناحیه هیپوکامپ مدل سندرم جنین الکلی

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه زیست شناسی، واحد دامغان، دانشگاه آزاد اسلامی، دامغان، ایران

2 گروه فیزیولوژی، دانشگاه علوم پزشکی شاهرود، شاهرود، ایران

چکیده

پژوهش ­های آزمایشی و بالینی نشان داده که قرارگرفتن در معرض الکل پس از تولد باعث التهاب در هیپوکامپ در بین سایر مناطق مغزی می­ شود. از طرفی دیگر مصرف الکل در طول بارداری موجب فعال­ سازی اکسیداتیو التهابی به همراه آپوپتیک وسیع بیماری نورودژنراتیو در نواحی مغزی خواهد شد به علاوه نقص عصبی ناشی از الکل در فرزندان با فعال شدن آبشار اکسیداتیو التهابی همراه با نیتروژن­ دهی گسترده­ و آپوپتوز در مناطق مغزی مختلف مانند هیپوکامپ می ­باشد. کروسین عمده ­ترین ماده­ موثره و عامل ایجاد رنگ در زعفران است که دارای اثرات آنتی ­اکسیدانی، ضد التهابی و ضد آپوپتیک است و می‌تواند از اعصاب محافظت کند. این تحقیق با هدف بررسی اثر تجویز کروسین بر اختلالات حافظه و مرگ سلولی نکروز ناحیه هیپوکامپ مدل سندرم جنین الکلی انجام شد. تعداد 72 سر نوزاد نر موش صحرایی نر روز دوم پس از تولد، به شکل تصادفی به شش گروه (12 سر در هر گروه) شامل کنترل، گروه شم، گروه اتانول و گروه ­های اتانول+تیمار با کروسین )دوزهای 15، 30 و  45 میلی ­گرم بر کیلوگرم) تقسیم شدند. از روز دوم تا دهم تولد، اتانول را با دوز 5/25 گرم بر کیلوگرم محلول در شیرخشک که به دو دوز 2/62 گرم بر کیلوگرم تقسیم شده بود، دو بار در روز و به فاصله دو ساعت با روش گاواژ دریافت نمودند. با استفاده از روش آزمون شیئی جدی، حافظه وابسته به هیپوکامپ و یادگیری فاصله‌­ای در ۳۶ روز پس از تولد ارزیابی گردید. هم چنین از رنگ ­آمیزی نیسل برای ارزیابی مرگ سلولی استفاده شد. نتایج مطالعه حاضر بیان نمود که تجویز کروسین به شکل معنی‌داری نقص شناختی ناشی از اتانول را کاهش داد (0/01>p). هم چنین با تجویز کروسین مرگ سلولی نکروتیک القاء شده به واسطه اتانول به شکل معنی­ داری کاهش یافت (0/01>p). بر اساس اثرات حفاظتی کروسین در مقابل سمیت نورونی ناشی از اتانول در مدل سندرم جنین الکلی، این ماده می‌تواند به عنوان یک درمان بالقوه برای عوارض ناشی از اتانول در دوران تکوین مطرح باشد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

The Effect of Crocin on Cognition and Necrosis Cell Death in the Hippocampus Area in the Model of Fetal Alcohol Spectrum Disorders in Male Rats

نویسندگان [English]

  • Lida Farhadi 1
  • Vida Hojati 1
  • Mehdi Khaksari 2
  • Gholamhassan Vaezi 1
1 Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
2 Department of Physiology, Shahroud University of Medical Sciences, Shahroud, Iran
چکیده [English]

Experimental and clinical studies have shown that postpartum alcohol exposure causes inflammation in the hippocampus among other areas of the brain. On the other hand, alcohol consumption during pregnancy will cause inflammatory oxidative activation along with extensive apoptotic neurodegenerative disease in brain areas. Different areas of the brain are like the hippocampus. Crocin is the main active ingredient and dye in saffron, which has antioxidant, anti-inflammatory and anti-apoptotic effects and can protect the nerves. The aim of this study was to evaluate the effect of crocin administration on memory disorders and cell death of necrosis of the hippocampus in the model of alcoholic fetal syndrome. 72 male neonates of male rats on the second day after birth, randomly divided into six groups (12 in each group) including control, sham group, ethanol group and ethanol + Crocin treatment groups) doses of 15, 30 and 45 mg/kg). From the second to the tenth day of birth, ethanol was received at a dose of 5.25 g/kg of milk powder solution, which was divided into two doses of 2.62 g/kg, twice a day for two hours by gavage. Using the novel object recognition test, hippocampal-dependent memory and distance learning were assessed at 36 days after birth. Nissel staining was also used to evaluate cell death. The results of the present study showed that crocin administration significantly reduced ethanol-induced cognitive deficits (p<0.01). Ethanol-induced necrotic cell death was also significantly reduced by crocin administration (p<0.01). Protective effects of Crocin against ethanol-induced neurotoxicity in the model of alcoholic fetal syndrome, this substance can be considered as a potential treatment for ethanol-induced complications during development.

کلیدواژه‌ها [English]

  • Crocin
  • Alcohol
  • Memory
  • Apoptosis
  • Necrosis

مراجع

  1. Wozniak, J.R., Riley, E.P. and Charness, M.E., Clinical presentation, diagnosis, and management of fetal alcohol spectrum disorder. The Lancet Neurology. 18: 760-770.
  2. Goodfellow, M.J., Abdulla K.A. and Lindquist D.H., 2016. Lindquist DH. Neonatal ethanol exposure impairs trace fear conditioning and alters NMDA receptor subunit expression in adult male and female rats. Alcoholism: Clinical and Experimental Research. 40: 309-318.
  3. Li, E., Deng, H., Wang, B., Fu, W., You, Y. and Tian, S., Apelin-13 exerts antidepressant like and recognition memory improving activities in stressed rats. European Neuropsychopharmacology. 26: 420-430.
  4. Akhondzadeh, S., Tahmacebi‐Pour, N., Noorbala, A.A., Amini, H., Fallah‐Pour, H. and Jamshidi, A.H., Crocus sativus L. in the treatment of mild to moderate depression: a double‐blind, randomized and placebo controlled trial. Phytotherapy Research. 19: 148-158.
  5. Niedzwiedz-Massey, V.M., Douglas J.C., Rafferty T., Wight P.A., Kane C.J.M. and Drew, P.D., 2021. Ethanol modulation of hippocampal neuroinflammation, myelination, and neurodevelopment in a postnatal mouse model of fetal alcohol spectrum disorders. Neurotoxicology and Teratology. 87: 107-115.
  6. Gustas, K., Li, L., Newville, J. and Cunningham, L.A., 2020. Functional and structural correlates of impaired enrichment-mediated adult hippocampal neurogenesis in a mouse model of prenatal alcohol exposure. Brain Plasticity. 6: 67-82.
  7. Barr, A.M., Hofmann, C.E., Phillips, A.G., Weinberg, J. and Honer, W.G., 2005. Prenatal ethanol exposure in rats decreases levels of complexin proteins in the frontal cortex. Alcoholism: Clinical and Experimental Research. 29:
    1915-1920.
  8. Sebastiani, G., Borrás-Novell, C., Casanova, M.A., Pascual, Tutusaus, M., Ferrero Martínez, S., Gómez Roig, M.D. and García-Algar, O., 2018. The effects of alcohol and drugs of abuse on maternal nutritional profile during pregnancy. Nutrients. 10: 1008.
  9. Lueptow, L.M., 2017. Novel object recognition test for the investigation of learning and memory in mice. Journal of Visualized Experiments. 126: e55718.
  10. Fryer, S.L., Tapert, S.F., Mattson, S.N., Paulus, M.P., Spadoni, A.D. and Riley, E.P., 2007. Prenatal alcohol exposure affects frontal-striatal BOLD response during inhibitory control. Alcoholism: Clinical and Experimental Research. 31: 1415-1424.
  11. Brocardo, P.S., Gil‐Mohapel, J., Wortman, R., Noonan, A., McGinnis, E. and Patten, A.R., 2017. The effects of ethanol exposure during distinct periods of brain development on oxidative stress in the adult rat brain. Alcoholism: Clinical and Experimental Research. 41: 26-37.
  12. Helfer, J.L., Goodlett, C.R., Greenough, W.T. and Klintsova, A.Y., 2009. The effects of exercise on adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure during the brain growth spurt. Brain Research. 1294: 1-11.
  13. Hunt, P.S. and Barnet, R.C., 2015. An animal model of fetal alcohol spectrum disorder: Trace conditioning as a window to inform memory deficits and intervention tactics. Physiology and Behavior. 148: 36-44.
  14. Michaelian, K. and Sutton, , 2013. Distributed cognition and memory research: History and current directions. Review of Philosophy and Psychology. 4: 1-24.
  15. Ahmadnezhad, M., Khodadadi, S., Nasiri Khalili, M.A. and Maleksabet, N., 2020. Evaluation of chronic stress on spatial memory using Morris water maze test in animal model. Journal of Animal Environment. 12: 179-186.
  16. Amiri, B. and Mohammadzadeh M., 2015. Memory enhancement in induced diabetic rats fed with the organic chromium enriched in unicellular yeasts. Journal of Animal Environment. 7: 59-64.
  17. Toosi, A., Shajiee, H., Khaksari, M., Vaezi, and Hojati, V., 2019. Obestatin improve spatial memory impairment in a rat model of fetal alcohol spectrum disorders via inhibiting apoptosis and neuroinflammation. Neuropeptides. 74: 88-94.
  18. Jafari, M., Hojati, V., Khaksari, M. and Vaezi, G., 2021. Simvastatin attenuates spatial memory impairment via inhibiting microgliosis and apoptotic cell death against ethanol induced neurotoxicity in the developing rat hippocampus. Brain Research. 1758: 1-9.
  19. Klintsova, A.Y., Helfer, J.L., Calizo, L.H., Dong, W.K., Goodlett, C.R. and Greenough, W.T., 2007. Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure. Alcoholism: Clinical and Experimental Research. 31: 2073-2082.
  20. Hamilton, G., Criss, K. and Klintsova, A., Voluntary exercise partially reverses neonatal alcohol‐induced deficits in mPFC layer II/III dendritic morphology of male adolescent rats. Synapse. 69: 405-415.
  21. Noori-Daloii, M.R. and Yaghoobi M.M., Apoptosis and its relation to cancer, Part II. Journal of Razi. 2: 18-36.
  22. Ghotbeddin, Z., Tabandeh, M.R., Borujeni M.P., Truski F.F. and Tabrizian L., Study the effect of crocin in three maternal hypoxia protocols with different oxygen intensities on motor activity and balance in rat offspring. Acta Neurologica Belgica. 120: 155-161.
  23. Ghotbeddin, Z., Tabandeh, M.R., Pourmahdi Borujeni, M., Fahimi Truski, F., Zalaki GhorbaniPour, M.R. and Tabrizian, L., 2021. Crocin mitigated cognitive impairment and brain molecular alterations induced by different intensities of prenatal hypoxia in neonatal rats. Brain Behavior. 11: e02078.
  24. McLachlan, K., Flannigan, K., Temple, V., Unsworth, K. and Cook, J.L., 2020. Difficulties in daily living experienced by adolescents, transition‐aged youth, and adults with fetal alcohol spectrum disorder. Alcoholism: Clinical and Experimental Research. 44: 1609-1624.
  25. Mihalick, S.M., Crandall, J.E., Langlois, J.C., Krienke, J.D. and Dube, W.V., 2001. Prenatal ethanol exposure, generalized learning impairment, and medial prefrontal cortical deficits in rats. Neurotoxicology and Teratology. 23: 453-462.
  26. Jacobson, S.W., Hoyme, H.E., Carter, R.C., Dodge, N.C., Molteno, C.D., Meintjes, E.M. and Jacobson, J.L., Evolution of the Physical Phenotype of Fetal Alcohol Spectrum Disorders from Childhood through Adolescence. Alcoholism: Clinical and Experimental Research. 45: 395-408.
  27. Lawrence, R.C., Otero, N.K. and Kelly, S.J., 2012. Selective effects of perinatal ethanol exposure in medial prefrontal cortex and nucleus accumbens. Neurotoxicology and Teratology. 34: 128-135.
  28. Kelly, S.J., Goodlett, C.R. and Hannigan, J.H., 2009. Animal models of fetal alcohol spectrum disorders: impact of the social environment. Developmental Disabilities Research Reviews. 15: 200-208.
  29. Ethen, M.K., Ramadhani, T.A., Scheuerle, A.E., Canfield, M.A., Wyszynski, D.F., Druschel, C.M. and Romitti, P.A., 2009. Alcohol consumption by women before and during pregnancy. Matern Child Health Journal. 13: 274-285.
  30. Gadami, S., Gadami, M.R., Haghighizad, H., Pourmotabbed, A., Sahraei, H. and Kamal nejad, M., 2016. Investigating the effect of saffron extract on learning and spatial memory in rats. The 18th Congress of Physiology and Pharmacology of Iran. (In Persian)
  31. Hosseinzadeh, H. and Ziaeei, S.T., 2015. Investigating the effect of saffron and its active ingredients, safranal and crocin, on healthy and hyoscine-destroyed memory on spatial learning in rats. Medicinal Plants. 5: 40-50. (In Persian)
  32. Hosseinzadeh, H., Abnous, Kh., Razavi, B.M. and Behrvanfar, N., 2014. Investigating the effects of crocin on hisosin-degraded memory on spatial learning and its effect on the level of BDNF, CREB and P-CREB proteins in the rat brain. The first international congress of physiology and pharmacology and the 22nd congress of physiology and pharmacology of Iran. (In Persian)
  33. Haghighizad, H., Pourmotabbed, A., Gadami, M.R., Gadami, S., Sahraei, H. and Nedaeei, S.A., 2016. The effect of saffron aqueous extract on the destruction of learning and spatial memory caused by morphine. The 18th Congress of Physiology and Pharmacology of Iran. (In Persian)
  34. Sohrabi Asadabad, J., Ghotbeddin, Z. and Tabandeh, M.R., 2017. Study the Effect of Crocin on Avoidance Memory and Motor Activity Impairment Induced by Doxorubicin Administration in Adult Male Rats. Arak Medical University Journal. 20(126): 45-56. (In Persian)
  35. Naghizadeh, B., Mansouri, S.M.; Gorbanzadeh, B., Farbod, Y. and Sarkaki, A., 2013. Investigating the protective effects of oral administration of crocin on spatial memory deficits and oxidative damage caused by streptozotocin in rats. The 21st Congress of Physiology and Pharmacology of Iran. (In Persian)
  36. Rajaei, Z., Alai, H. and Hosseini, S.M., 2014. The effect of crocin on motor behavior and oxidative stress in the striatum region of the brain in an experimental model of Parkinson's disease. The first international congress of physiology and pharmacology and the 22nd congress of physiology and pharmacology of Iran. (In Persian)
  37. Allan, A.M., Chynoweth, J., Tyler, L.A. and Caldwell, K.K., 2003. A mouse model of prenatal ethanol exposure using a voluntary drinking paradigm. Alcoholism: Clinical and Experimental Research. 27: 2009-2016.
  38. Johnson, T.B. and Goodlett, C.R., Selective and enduring deficits in spatial learning after limited neonatal binge alcohol exposure in male rats. Alcoholism: Clinical and Experimental Research. 26: 83-93.
فصلنامه محیط زیست جانوری
دوره 14، شماره 3
آبان 1401
صفحه 103-110

فایل ها

هم رسانی

ارجاع به این مقاله

آمار