تأثیر استروژن‌درمانی بر اختلال عملکرد شناختی ناشی از تخریب هسته‌ی قاعده‌ای مگنوسلولاریس: مدل حیوانی بیماری آلزایمر

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی دکتری، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه شهید چمران اهواز، اهواز، ایران

2 استاد، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه شهید چمران اهواز، اهواز، ایران

3 استاد، مرکز تحقیقات علوم اعصاب، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران

4 دانشیار گروه زیست شناسی دانشکده علوم دانشگاه شهید چمران اهواز، اهواز، ایران

5 استادیار، گروه آمار، دانشکده‌ی علوم ریاضی و کامپیوتر، دانشگاه شهید چمران اهواز، اهواز، ایران

چکیده

مقدمه: عملکردهای شناختی با افزایش سن و به مرور زمان کاهش می‌یابد که شاید به خاطر نقص عملکرد کولینرژیک در قاعده‌ی مغز جلویی باشد. با توجه به اهمیت فیزیولوژیک تأثیر سریع استروژن، این تحقیق با هدف ارزیابی اثر 17-β استرادیول بر تخریب دو طرفه‌ی هسته‌ی قاعده‌ای مگنوسلولاریس مو‌ش‌های صحرایی نر بالغ مدل بیماری آلزایمر انجام شد.روش‌ها: در این مطالعه، 40 سر موش‌ صحرایی نر بالغ نژاد ویستار (Wistar) به شش گروه هشت‌تایی تقسیم شدند. گروه شاهد (دست نخورده)، گروه تخریب Nucleus basalis of meynert (NBM) (تخریب دو طرفه‌ی هسته‌ی قاعده‌ای مگنوسلولاریس با القای جریان الکتریکی 5/0 میلی‌آمپر به مدت 3 ثانیه)، گروه شاهد تخریب (ورود الکترود به هسته‌ی NBM بدون القای جریان الکتریکی)، گروه استروژن (تخریب NBM + 45 میکروگرم بر کیلوگرم 17-β استرادیول)، گروه روغن کنجد (تخریب NBM + 200 میکرولیتر روغن کنجد). در آزمون‌های اکتساب و یادآوری دستگاه ماز شعاعی هشت بازویی، الگوهای ورود به بازوها در هر گروه برای محاسبه‌ی انتخاب‌های درست، خطاهای حافظه‌ی کارکردی، خطاهای حافظه‌ی مرجع و زمان سپری شده در نظر گرفته شد.یافته‌ها: تخریب دو طرفه‌ی هسته‌ی NBM، کاهش حافظه‌ی فضایی در آزمون اکتساب را به شکل افزایش معنی‌داری در خطای حافظه‌ی کارکردی و مرجع (001/0 > P) و همچنین کاهش این عملکردها در آزمون یادآوری (001/0 > P) را نسبت به گروه شاهد تخریب نشان داد. تزریق 17-β استرادیول (45 میکروگرم برکیلوگرم) بعد از تخریب NBM، پارامترهای خطاهای حافظه‌ی فضایی را در دو آزمون اکتساب و یادآوری نسبت به گروه شاهد تخریب بهبود بخشید (050/0 < P).نتیجه‌گیری: تخریب الکتریکی NBM می‌تواند عملکرد حافظه‌ی فضایی را کاهش دهد. استروژن‌درمانی بعد از آسیب مغزی اختلال شناختی را بهبود داد.

کلیدواژه‌ها

عنوان مقاله [English]

Effects of Estrogen Therapy on Cognitive Performance Deficit Induced by Nucleus Basalis Magnocellularis Lesion: Animal Model of Alzheimer’s Disease

نویسندگان [English]

  • Neda Dabir 1
  • Ahmadali Moazedi 2
  • Abbas Haghparast 3
  • Lotfollah Khajepour 4
  • Mohammadreza Akhoond 5
1 PhD Student, Department of Biology, School of Sciences, Shahid Chamran University, Ahwaz, Iran
2 Professor, Department of Biology, School of Sciences, Shahid Chamran University, Ahwaz, Iran
3 Professor, Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Associate Professor, Department of Biology, School of sciences, Shahid Chamran University, Ahwaz, Iran
5 Assistant Professor, Department of Statistics, School of Mathematical Science and Computer, Shahid Chamran University, Ahwaz, Iran
چکیده [English]

Background: Cognitive performance appears to diminish with age and passing of time, probably due to the basal forebrain cholinergic dysfunction. Given the physiological significance of the acute effect of estrogen, this study was conducted aiming to investigate the effect of 17β-estradiol treatment on cognitive performance in nucleus basalis magnocellularis (NBM) induced lesions.Methods: In this experimental study, 40 adult male Wistar rats were divided into five different groups (8 rat in each group): Control (intact), NBM lesion group, which received electrically-induced lesion (0.5 mA, 3s) in NBM, Sham group (the electrode was impaled into the NBM with no lesion), Estrogen group (lesion+45μg/kg 17β-estradiol) and Vehicle group (NBM lesion+200μl sesame oil). Acquisition and retention testing was done using an eight-radial arm maze, in which, the patterns of arm entries in each group was recorded for calculating correct choices, working memory errors, reference memory errors and latency.Findings: Bilateral NBM lesion showed the reduction of spatial memory acquisition in the form of increased working and reference memory errors (P < 0.001). It further reduced these functions in retention testing (P < 0.001) compared to the control group. Post-lesion treatment with 45 μg/kg estrogen improved the parameters of spatial memory errors in the acquisition and retention tasks comparing to the Sham group (P > 0.05).Conclusion: Electrical NBM lesion can reduce spatial memory function. Estrogen therapy after brain injury improved cognitive disorder.

کلیدواژه‌ها [English]

  • Alzheimer’s disease
  • Basal forebrain
  • Cognitive performance
  • Nucleus Basalis Magnocellularis
  • Estrogen Therapy

مراجع

  1. Iadecola C, Anrather J. Stroke research at a crossroad: asking the brain for directions. Nat Neurosci 2011; 14(11): 1363-8.
  2. Thathiah A, de Strooper B. G protein–coupled receptors, cholinergic dysfunction, and Aß toxicity in Alzheimer's disease. Sci Signal 2009; 2(93): 8.
  3. Hardenacke K, Kuhn J, Lenartz D, Maarouf M, Mai JK, Bartsch C, et al. Stimulate or degenerate: deep brain stimulation of the nucleus basalis Meynert in Alzheimer dementia. World Neurosurg 2013; 80(3-4): S27-S43.
  4. Fisher A. Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer's disease. J Neurochem 2012; 120(Suppl 1): 22-33.
  5. Nyakas C, Granic I, Halmy LG, Banerjee P, Luiten PG. The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-beta42 with memantine. Behav Brain Res 2011; 221(2): 594-603.
  6. Ovsepian SV, Herms J. Drain of the brain: low-affinity p75 neurotrophin receptor affords a molecular sink for clearance of cortical amyloid beta by the cholinergic modulator system. Neurobiol Aging 2013; 34(11): 2517-24.
  7. Auld DS, Kornecook TJ, Bastianetto S, Quirion R. Alzheimer's disease and the basal forebrain cholinergic system: Relations to beta-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 2002; 68(3): 209-45.
  8. Abraham IM, Koszegi Z, Tolod-Kemp E, Szego EM. Action of estrogen on survival of basal forebrain cholinergic neurons: promoting amelioration. Psychoneuroendocrinology 2009; 34(Suppl 1): S104-S112.
  9. Raghanti MA, Simic G, Watson S, Stimpson CD, Hof PR, Sherwood CC. Comparative analysis of the nucleus basalis of Meynert among primates. Neuroscience 2011; 184: 1-15.
  10. Dumas JA, Newhouse PA. The cholinergic hypothesis of cognitive aging revisited again: cholinergic functional compensation. Pharmacol Biochem Behav 2011; 99(2): 254-61.
  11. Sarter M, Gehring WJ, Kozak R. More attention must be paid: the neurobiology of attentional effort. Brain Res Rev 2006; 51(2): 145-60.
  12. Hasselmo ME, Sarter M. Modes and models of forebrain cholinergic neuromodulation of cognition. Neuropsychopharmacology 2011; 36: 52-73.
  13. Newhouse P, Dumas J. Estrogen-cholinergic interactions: Implications for cognitive aging. Horm Behav 2015; 74: 173-85.
  14. Daniel JM. Estrogens, estrogen receptors, and female cognitive aging: the impact of timing. Horm Behav 2013; 63(2): 231-7.
  15. McClure RE, Barha CK, Galea LA. 17beta-Estradiol, but not estrone, increases the survival and activation of new neurons in the hippocampus in response to spatial memory in adult female rats. Horm Behav 2013; 63(1): 144-57.
  16. Miller MM, Hyder SM, Assayag R, Panarella SR, Tousignant P, Franklin KB. Estrogen modulates spontaneous alternation and the cholinergic phenotype in the basal forebrain. Neuroscience 1999; 91(3): 1143-53.
  17. Ishunina TA, Swaab DF. Increased expression of estrogen receptor alpha and beta in the nucleus basalis of Meynert in Alzheimer's disease. Neurobiol Aging 2001; 22(3): 417-26.
  18. Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, et al. Brain estrogen deficiency accelerates Aß plaque formation in an Alzheimer's disease animal model. Proc Natl Acad Sci U S A 2005; 102(52): 19198-203.
  19. Gibbs RB. Estrogen therapy and cognition: a review of the cholinergic hypothesis. Endocr Rev 2010; 31(2): 224-53.
  20. Szigeti C, Bencsik N, Simonka AJ, Legradi A, Kasa P, Gulya K. Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: a model for Alzheimer's disease. Brain Res Bull 2013; 94: 9-16.
  21. Inagaki T, Etgen AM. Neuroprotective action of acute estrogens: animal models of brain ischemia and clinical implications. Steroids 2013; 78(6): 597-606.
  22. Davis CP, Franklin LM, Johnson GS, Schrott LM. Prenatal oxycodone exposure impairs spatial learning and/or memory in rats. Behav Brain Res 2010; 212(1): 27-34.
  23. MacLusky N, Luine VN, Hajszan T, Leranth C. The 17a and 17ß isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats. Endocrinology 2013; 146(1): 287-93.
  24. Montero-Pastor A, Vale-Martinez A, Guillazo-Blanch G, Marti-Nicolovius M. Effects of electrical stimulation of the nucleus basalis on two-way active avoidance acquisition, retention, and retrieval. Behav Brain Res 2004; 154(1): 41-54.
  25. 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. Physiol Pharmacol 2011, 14(4): 416-25.
  26. White NM, Milner PM. The psychobiology of reinforcers. Annu Rev Psychol 1992; 43: 443-71.
  27. Luine VN, Frankfurt M. Estrogens facilitate memory processing through membrane mediated mechanisms and alterations in spine density. Front Neuroendocrinol 2012; 33(4): 388-402.
  28. Cosquer B, Vasconcelos AP, Frohlich J, Cassel JC. Blood-brain barrier and electromagnetic fields: effects of scopolamine methylbromide on working memory after whole-body exposure to 2.45 GHz microwaves in rats. Behav Brain Res 2005; 161(2): 229-37.
  29. Bayat M, Baluchnejadmojarad T, Roghani M, Goshadrou F, Ronaghi A, Mehdizadeh M. Netrin-1 improves spatial memory and synaptic plasticity impairment following global ischemia in the rat. Brain Res 2012; 1452: 185-94.
  30. Baddeley A. Working memory: Looking back and looking forward. Nature Reviews Neuroscience 2003; 4(10): 829-39.
  31. Verhaeghen P, Marcoen A, Goossens L. Facts and fiction about memory aging: A quantitative integration of research findings. J Gerontol 1993; 48(4): 157-71.
  32. White NM, McDonald RJ. Multiple parallel memory systems in the brain of the rat. Neurobiol Learn Mem 2002; 77(2): 125-84.
  33. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. Cambridge, MA: Academic Press; 2007.
  34. Rafii MS, Aisen PS. Advances in Alzheimer's disease drug development. BMC Medicine 2015; 13: 62.
  35. Paleja M, Girard TA, Herdman KA, Christensen BK. Two distinct neural networks functionally connected to the human hippocampus during pattern separation tasks. Brain Cogn 2014; 92C: 101-11.
  36. Murray CL, Fibiger HC. Learning and memory deficits after lesions of the nucleus basalis magnocellularis: reversal by physostigmine. Neuroscience 1985; 14(4): 1025-32.
  37. Miranda MI, Bermudez-Rattoni F. Reversible inactivation of the nucleus basalis magnocellularis induces disruption of cortical acetylcholine release and acquisition, but not retrieval, of aversive memories. Proc Natl Acad Sci USA 1999; 96(11): 6478-82.
  38. Sos-Hinojosa H, Guillazo-Blanch G, Vale-Martinez A, Nadal R, Morgado-Bernal I, Marti-Nicolovius M. Parafascicular electrical stimulation attenuates nucleus basalis magnocellularis lesion-induced active avoidance retention deficit. Behav Brain Res 2003; 144(1-2): 37-48.
  39. Givens B, Olton DS. Local modulation of basal forebrain: effects on working and reference memory. J Neurosci 1994; 14(6): 3578-87.
  40. Durkin TP, Cazala P, Garcia R. Transynaptic mechanisms controlling cholinergic neuronal activation in the septohippocampal and nBM-cortical pathways: differential roles in memory and attentional processes? In: Numan R, editor. The behavioral neuroscience of the septal region. Berlin, Germany: Springer Science and Business Media; 2000. p. 146-74.
  41. Sabbatini M, Coppi G, Maggioni A, Olgiati V, Panocka I, Amenta F. Effect of lesions of the nucleus basalis magnocellularis and of treatment with posatirelin on cholinergic neurotransmission enzymes in the rat cerebral cortex. Mech Ageing Dev 1998; 104(2): 183-94.
  42. Mufson EJ, Counts SE, Fahnestock M, Ginsberg SD. Cholinotrophic molecular substrates of mild cognitive impairment in the elderly. Curr Alzheimer Res 2007; 4(4): 340-50.
  43. Bora SH, Liu Z, Kecojevic A, Merchenthaler I, Koliatsos VE. Direct, complex effects of estrogens on basal forebrain cholinergic neurons. Exp Neurol 2005; 194(2): 506-22.
  44. Perez-Alvarez MJ, Maza MC, Anton M, Ordonez L, Wandosell F. Post-ischemic estradiol treatment reduced glial response and triggers distinct cortical and hippocampal signaling in a rat model of cerebral ischemia. J Neuroinflammation 2012; 9: 157.
  45. Bimonte HA, Hyde LA, Hoplight BJ, Denenberg VH. In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze. Physiol Behav 2000; 70(3-4): 311-7.
  46. Hasegawa Y, Hojo Y, Kojima H, Ikeda M, Hotta K, Sato R, et al. Estradiol rapidly modulates synaptic plasticity of hippocampal neurons: Involvement of kinase networks. Brain Res 2015; 1621: 147-61.
  47. Woolley CS. Acute effects of estrogen on neuronal physiology. Annu Rev Pharmacol Toxicol 2007; 47: 657-80.
  48. Wilson IA, Puolivali J, Heikkinen T, Riekkinen P. Estrogen and NMDA receptor antagonism: effects upon reference and working memory. Eur J Pharmacol 1999; 381(2-3): 93-9.
  49. Roepke TA, Ronnekleiv OK, Kelly MJ. Physiological consequences of membrane-initiated estrogen signaling in the brain. Front Biosci (Landmark Ed) 2011; 16: 1560-73.
مجله دانشکده پزشکی اصفهان
دوره 34، شماره 370 - شماره پیاپی 370
فروردین و اردیبهشت 1395
صفحه 64-73

فایل ها

سابقه مقاله

  • تاریخ دریافت: 10 آبان 1394
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

هم رسانی

ارجاع به این مقاله

آمار