بررسی تأثیر اواریکتومی بر حافظه‌ی شناختی و یادگیری در موش‌های صحرایی مدل آلزایمری القا شده با اسکوپولامین

نوع مقاله : Original Article(s)

نویسندگان

1 کارشناسی ارشد، مرکز تحقیقات علوم اعصاب، دانشگاه علوم پزشکی ایران، تهران، ایران

2 دانشجو کارشناسی ارشد، کمیته‌ی تحقیقات دانشجویی، دانشگاه علوم پزشکی ایران، تهران، ایران

3 دانشجو دکتری، گروه آناتومی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی ایران، تهران، ایران

10.48305/jims.v42.i792.1027

چکیده

مقاله پژوهشی




مقدمه: بیماری آلزایمر (Alzheimer's disease) AD، یک بیماری پیشرونده و جزء شایع‌ترین اختلالات نورودژنراتیو می‌باشد. بیماری آلزایمر باعث اختلال در حافظه، یادگیری و سایر عملکردهای مهم ذهنی می‌شود. هدف این مطالعه، تأثیر اورایکتومی بر حافظه‌ی شناختی و یادگیری در مدل موش AD القا شده با اسکوپولامین می‌باشد.
روش‌ها: در مطالعه‌ی حاضر 32 موش صحرایی ماده نژاد ویستار (وزن 180 تا 200 گرم) در چهار گروه شاهد، اواریکتومی (OVX)، آلزایمری (AD) و اواریکتومی + آلزایمری (AD+OVX) تقسیم شد. مدل آلزایمری توسط تزریق اسکوپولامین، mg/kg 1 بصورت داخل صفاقی به مدت 14 روز القا شد. حافظه‌ی کوتاه‌مدت و یادگیری غیر اجتنابی به ترتیب توسط آزمون رفتاری ماز Y شکل و شاتل باکس ارزیابی شد. برای ارزیابی میزان تخریب نورونی در ناحیه‌ی CA1 نمونه‌های بافت هیپوکمپ از روش رنگ‌آمیزی نیسل استفاده گردید. داده‌ها توسط آزمون ANOVA یک‌طرفه و آزمون تقریبی Tukey در سطح معنی‌داری 05/0 آنالیز گردید.
یافته‌ها: بر طبق آزمون ماز، شاخص درصد تناوب در گروه OVX، AD و AD+OVX کاهش معنی‌داری نسبت به گروه شاهد مشاهده شد. بر اساس آزمون شاتل باکس، میانگین مدت ورود به ناحیه‌ی تاریک در گروه OVX، AD و AD+OVX کاهش معنی‌داری نسبت به گروه شاهد مشاهده شد. نتایج رنگ‌آمیزی نیسل نشان داد که میانگین تعداد سلول‌های زنده در گروه OVX، AD و AD+OVX نسبت به گروه شاهد کاهش معنی‌‌داری داشت.
نتیجه‌گیری: محرومیت از استروژن ناشی از OVX می‌تواند اثرات تشدید کننده‌ای در علایم ناشی از آلزایمر بر حافظه‌ی شناختی، یادگیری و همچنین آسیب نورونی داشته باشد.

تازه های تحقیق

رشاد رضاپور:  Google Scholar 

افسانه جابری اصل: Google Scholar, PubMed

کلیدواژه‌ها


عنوان مقاله [English]

Investigating the Effect of Ovariectomy on Cognitive Memory and Learning in Scopolamine-Induced Alzheimer's Model Rats

نویسندگان [English]

  • Reshad Rezapour 1
  • Hiva Osmani 2
  • Afsaneh Jaberi-Asl 3
1 MSc, Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran
2 MSc Student, Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
3 PhD Candidate, Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
چکیده [English]

Background: Alzheimer's disease (AD) is a progressive disease and one of the most common neurodegenerative disorders. AD causes impairment in memory, learning and other important mental functions. The aim of this study is the effect of ovariectomy on cognitive memory and learning in AD mouse model induced with scopolamine.
Methods: In the present study, 32 female Wistar rats (weight 180 to 200 grams) were divided into four groups: control, ovariectomy (OVX), Alzheimer's disease (AD), and ovariectomy + Alzheimer's disease (AD+OVX). Alzheimer's model was induced by intraperitoneal injection of scopolamine, 1 mg/kg for 14 days. Short-term memory and non-avoidance learning were evaluated by Y-shaped maze and shuttle box behavioral tests, respectively. Nissel's staining method was used to evaluate the degree of neuronal destruction in the CA1 area of hippocampal tissue samples. Data were analyzed by one-way ANOVA and Tukey's approximate test at a significance level of 0.05.
Findings: According to the Maze test, a significant decrease in frequency index was observed in the OVX, AD and AD+OVX groups compared to the control group. According to the shuttle box test, the average duration of entering the dark area in the OVX, AD and AD+OVX groups was significantly reduced compared to the control group. The Nissl staining results showed that the average number of live cells in the OVX, AD and AD+OVX groups was significantly reduced compared to the control group.
Conclusion: Deprivation of estrogen caused by OVX can have aggravating effects on Alzheimer's symptoms on cognitive memory, learning and also neuronal damage.

کلیدواژه‌ها [English]

  • Ovariectomy
  • Memory
  • Learning
  • Alzheimer's disease
  • Scopolamine
  1. Yeung ST, Martinez-Coria H, Ager RR, Rodriguez-Ortiz CJ, Baglietto-Vargas D, LaFerla FM. Repeated cognitive stimulation alleviates memory impairments in an Alzheimer’s disease mouse model. Brain Res Bull 2015;117: 10-5.
  2. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener 2019; 14(1): 32.
  3. Sengoku R. Aging and Alzheimer's disease pathology. Neuropathology 2020; 40(1): 22-9.
  4. Garcia-Segura LM, Balthazart J. Steroids and neuroprotection: New advances. Front Neuroendocrinol 2009; 30(2): v-ix.
  5. Coughlan GT, Betthauser TJ, Boyle R, Koscik RL, Klinger HM, Chibnik LB, et al. Association of age at menopause and hormone therapy use with tau and β-amyloid positron emission tomography. JAMA Neurol 2023; 80(5): 462-73.
  6. Jameie SB, Pirasteh A, Naseri A, Jameie MS, Farhadi M, Babaee JF, et al. β-Amyloid Formation, Memory, and Learning Decline Following Long-term Ovariectomy and Its Inhibition by Systemic Administration of Apigenin and β-Estradiol. Basic Clin Neurosci 2021; 12(3): 383-94.
  7. Reuben R, McFall GP, Dixon RA, Einstein G. Predictors of Alzheimer’s disease risk in women with bilateral oophorectomy from the UK Biobank. Alzheimer's & Dementia 2022; 18(S11): e063188.
  8. Ding F, Yao J, Zhao L, Mao Z, Chen S, Brinton RD. Ovariectomy induces a shift in fuel availability and metabolism in the hippocampus of the female transgenic model of familial Alzheimer's. PLoS One 2013; 8(3): e59825.
  9. Bhavnani BR. Estrogens and menopause: pharmacology of conjugated equine estrogens and their potential role in the prevention of neurodegenerative diseases such as Alzheimer's. J Steroid Biochem Mol Biol 2003; 85(2-5): 473-82.
  10. Thiebaut C, Vlaeminck-Guillem V, Trédan O, Poulard C, Le Romancer M. Non-genomic signaling of steroid receptors in cancer. Mol Cell Endocrinol 2021; 538: 111453.
  11. Kuruca SE, Karadenizli S, Akgun-Dar K, Kapucu A, Kaptan Z, Uzum G. The effects of 17β-estradiol on blood brain barrier integrity in the absence of the estrogen receptor alpha; an in-vitro model. Acta Histochem 2017; 119(6): 638-47.
  12. Jett S, Malviya N, Schelbaum E, Jang G, Jahan E, Clancy K, et al. Endogenous and exogenous estrogen exposures: how women’s reproductive health can drive brain aging and inform Alzheimer’s prevention. Front Aging Neurosci 2022; 14: 831807.
  13. Frye CA, Duffy CK, Walf AA. Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task. Neurobiol Learn Mem 2007; 88(2): 208-16.
  14. Grissom EM, Daniel JM. Evidence for Ligand-Independent Activation of Hippocampal Estrogen Receptor-α by IGF-1 in Hippocampus of Ovariectomized Rats. Endocrinology 2016; 157(8): 3149-56.
  15. Farkas S, Szabó A, Török B, Sólyomvári C, Fazekas CL, Bánrévi K, et al. Ovariectomy-induced hormone deprivation aggravates Aβ(1-42) deposition in the basolateral amygdala and cholinergic fiber loss in the cortex but not cognitive behavioral symptoms in a triple transgenic mouse model of Alzheimer's disease. Front Endocrinol (Lausanne) 2022; 13: 985424.
  16. Aykac A, Ozbeyli D, Uncu M, Ertaş B, Kılınc O, Şen A, et al. Evaluation of the protective effect of Myrtus communis in scopolamine-induced Alzheimer model through cholinergic receptors. Gene 2019; 689: 194-201.
  17. Burgess A, Dubey S, Yeung S, Hough O, Eterman N, Aubert I, et al. Alzheimer disease in a mouse model: mr imaging–guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior. Radiology 2014; 273(3): 736-45.
  18. Shamsipour S, Sharifi G, Taghian F. Impact of interval training with probiotic (L. plantarum / Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer’s disease. Neurosci Lett 2021; 756: 135949.
  19. Goodarzi S, Pazirandeh A, Jameie SB, Baghban Khojasteh N. Differentiation in boron distribution in adult male and female rats' normal brain: A BNCT approach. Appl Radiat Isot 2012; 70(6): 952-6.
  20. Zhu Y, Liu F, Zou X, Torbey M. Comparison of unbiased estimation of neuronal number in the rat hippocampus with different staining methods. J Neurosci Methods 2015; 254: 73-9.
  21. Mandour DA, Bendary MA, Alsemeh AE. Histological and imunohistochemical alterations of hippocampus and prefrontal cortex in a rat model of Alzheimer like-disease with a preferential role of the flavonoid "hesperidin". J Mol Histol 2021; 52(5): 1043-65.
  22. Liu G, Wang J, Deng XH, Ma PS, Li FM, Peng XD, et al. The Anticonvulsant and Neuroprotective Effects of Oxysophocarpine on Pilocarpine-Induced Convulsions in Adult Male Mice. Cell Mol Neurobiol 2017; 37(2): 339-49.
  23. Ghofrani S, Joghataei M-T, Mohseni S, Baluchnejadmojarad T, Bagheri M, Khamse S, et al. Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms. Eur J Pharmacol 2015; 764: 195-201.
  24. Khaleghi M, Rajizadeh MA, Bashiri H, Kohlmeier KA, Mohammadi F, Khaksari M, et al. Estrogen attenuates physical and psychological stress-induced cognitive impairments in ovariectomized rats. Brain Behav 2021; 11(5): e02139.
  25. Fedotova JO, Hartmann G, Lénárd L, Sapronov N. Involvement of 5-HT1? receptors in passive avoidance learning in intact and ovariectomized female rats. Acta Physiologica Hungarica 2004; 91(3-4): 185-96.
  26. Hosseini N, Alaei H, Reisi P, Radahmadi M. The effect of treadmill running on passive avoidance learning in animal model of Alzheimer disease. Int J Prev Med 2013; 4(2): 187-92.
  27. Moazedi Aa, Moosavi M, Chinipardaz R. The effect of estrogen on passive avoidence memory in an experimental model of Alzheimer`s disease in male rats [in Persian]. Physiol Pharmacol 2011; 14(4): 416-25.
  28. Rashno M, Gholipour P, Salehi I, Komaki A, Rashidi K, Esmaeil Khoshnam S, et al. p-Coumaric acid mitigates passive avoidance memory and hippocampal synaptic plasticity impairments in aluminum chloride-induced Alzheimer's disease rat model. Journal of Functional Foods 2022; 94: 105117.
  29. Hu Z, Yang Y, Gao K, Rudd JA, Fang M. Ovarian hormones ameliorate memory impairment, cholinergic deficit, neuronal apoptosis and astrogliosis in a rat model of Alzheimer's disease. Exp Ther Med 2016; 11(1): 89-97.
  30. Luo M, Zeng Q, Jiang K, Zhao Y, Long Z, Du Y, et al. Estrogen deficiency exacerbates learning and memory deficits associated with glucose metabolism disorder in APP/PS1 double transgenic female mice. Genes Dis 2022; 9(5): 1315-31.