بررسی نقش گیرنده نوع 3- سروتونین در ناحیه CA1 هیپوکامپ مغز بر فراموشی ناشی از محرومیت 6 ساعته از خواب متناقض RSD) REM) و خواب کلی(TSD)

نوع مقاله : مقاله پژوهشی

نویسنده

مدرس-زیست شناسی-دانشگاه پیام نور-آموزش و پرورش

چکیده

زمینه و هدف: خواب یک حالت برگشت پذیر است که ظرفیت واکنش و تعامل با محیط را محدود می کند. گیرنده 5HT3 که بطور گسترده در ناحیه CA1 هیپوکامپ مغز بیان می شود، نقشی حیاتی در تنظیم خواب و تثبیت حافظه دارد. هدف این مطالعه بررسی تاثیر فعال سازی و غیرفعال سازی گیرنده 5HT3 به ترتیب با Y25130 و MCHL بر اختلال تثبیت حافظه تحت القای محرومیت از دو نوع خواب کلی total sleep deprivation)) وخواب متناقض REM sleep deprivation) ) در موش صحرایی بود.
روش بررسی: موشهای صحرایی نر نژاد ویستار بطور تصادفی درپنج گروه هشت تایی قرارگرفتند:1 –دو گروه دریافت کننده دوزهای موثر آگونیست و آنتاگونیست گیرنده 5HT3 2-  شاهد TSD، 3-با محرومیت از خواب TSD 4- شاهد RSD 5-با محرومیت از خواب .RSD
 از تکنیک چندسکویی برای القای RSD و تکنیک واتر باکس برای القای TSD و آزمون اجتناب غیرفعال برای ارزیابی تثبیت حافظه استفاده شده است.
یافته ها:  دوزهای 01/0 و 001/0 میلی گرم آگونیست گیرنده 5HT3  (MCHL) و دوز 1/0 میلی گرم آنتاگونیست گیرنده 5HT3 (Y25130)  بدون محرومیت از خواب باعث کاهش معنی دار حافظه اجتنابی  (P<0.01)شد. در حالی که MCHL با دوز1/0 و نیز Y25130 با دوزهای 1/0 و 01/0میلی گرم بطور معنی داری فعالیت حرکتی را افزایش دادند (P<0.01)، اما هر دو دارو درتمامی دوزها بر روی درد تاثیر معنی داری نداشتند. دوز زیر آستانه  Y25130 فراموشی ناشی از TSD و RSD را بطور معنی داری برگرداند (P<0.01). در حالی که هر دو دارو در شرایط TSD و RSD تاثیر معنی داری بر فعالیت حرکتی را نشان ندادند. اما MCHL  در شرایط RSD  و Y25130  در شرایط TSD بطور معنی داری بی دردی را افزایش دادند (P<0.01).
نتیجه گیری: بر اساس یافته های این تحقیق بنظر میرسد گیرنده های 5HT3 در ناحیهCA1 هیپوکامپ نقش حیاتی در رفتارهای شناختی و غیر شناختی ایجاد شده بوسیله TSD و RSD بازی می کنند.

کلیدواژه‌ها


1-Colavito V, Fabene PF, Grassi-Zucconi G, Pifferi F, Lamberty Y, Bentivoglio M, et al. Experimental sleep deprivation as a tool to test memory deficits in rodents. Frontiers in systems neuroscience. 2013;  7- 106. Dec 13;7:106. PubMed PMID: 24379759.
2-Kim Y, Elmenhorst D, Weisshaupt A, Wedekind F, Kroll T, McCarley RW, et al. Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain. Journal of sleep research. 2015 Oct;24(5):549-58. PubMed PMID: 25900125.
3-Graves L, Pack A, Abel T. Sleep and memory: a molecular perspective. Trends in neurosciences. 2001:237-43. PubMed PMID: 11250009.
4-Uschakov A, Grivel J, Cvetkovic-Lopes V, Bayer L, Bernheim L, Jones BE, et al. Sleep-deprivation regulates alpha-2 adrenergic responses of rat hypocretin/orexin neurons. PloS one. 2011;3-4. PubMed PMID: 21347440.
5-Jones DG, Endsley MR. Sources of situation awareness errors in aviation. Aviation, space, and environmental medicine. 1996:507-12. PubMed PMID: 8827130.
6-Westcott KJ. Modafinil, sleep deprivation, and cognitive function in military and medical settings. Military medicine. 2005:333-5. PubMed PMID: 15916305.
7-van Hulzen ZJ, Coenen AM. Paradoxical sleep deprivation and locomotor activity in rats. Physiology & behavior. 1981:741-4. PubMed PMID: 7323178.
8- Albertazzi P. Noradrenergic and serotonergic modulation to treat vasomotor symptoms. The journal of the British Menopause Society. 2006:7-11. PubMed PMID: 16513016.
9-Fink KB, Gothert M. 5-HT receptor regulation of neurotransmitter release. Pharmacological reviews. 2007:360-417. PubMed PMID: 18160701.
10-Chegini HR, Nasehi M, Zarrindast MR. Differential role of the basolateral amygdala 5-HT3 and 5-HT4 serotonin receptors upon ACPA-induced anxiolytic-like behaviors and emotional memory deficit in mice. Behavioural brain research. 2014:114-26. PubMed PMID: 24333573.
11-Raiteri M. Functional pharmacology in human brain. Pharmacological reviews. 2006 Jun;58(2):162-93. PubMed PMID: 16714485.
12-Ariel P, Ryan TA. New insights into molecular players involved in neurotransmitter release. Physiology. 2012:15-24. PubMed PMID: 22311967.
 13-Hampson RE, Deadwyler SA. Cannabinoids reveal the necessity of hippocampal neural encoding for short-term memory in rats. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2000:8932-42. PubMed PMID: 11102504.
14-Meneses A. Stimulation of 5-HT1A, 5-HT1B, 5-HT2A/2C, 5-HT3 and 5-HT4 receptors or 5-HT uptake inhibition: short- and long-term memory. Behavioural brain research. 2007:81-90. PubMed PMID: 17692935.
15-Prince TM, Abel T. The impact of sleep loss on hippocampal function. Learning & memory. 2013:558-69. PubMed PMID: 24045505. Pubmed Central PMCID: 3768199
16-Hakki Onen S, Alloui A, Jourdan D, Eschalier A, Dubray C. Effects of rapid eye movement (REM) sleep deprivation on pain sensitivity in the rat. Brain research. 2001:261-7. PubMed PMID: 11334806.
17-Zarrindast MR, Nasehi M, Pournaghshband M, Yekta BG. Dopaminergic system in CA1 modulates MK-801 induced anxiolytic-like responses. Pharmacology, biochemistry, and behavior. 2012:102-10. PubMed PMID: 22885281.
18-Naseri MH, Hesami-Tackallou S, Torabi-Nami M, Zarrindast MR, Nasehi M. Involvement of the CA1 GABAA receptors in MK-801-induced anxiolytic-like effects: an isobologram analysis. Behavioural pharmacology. 2014 Jun;25(3):197-205. PubMed PMID: 24710315.
19-Pierard C, Liscia P, Chauveau F, Coutan M, Corio M, Krazem A, et al. Differential effects of total sleep deprivation on contextual and spatial memory: modulatory effects of modafinil. 2011:399-405. PubMed PMID: 20883715
20-Pierard C, Liscia P, Philippin JN, Mons N, Lafon T, Chauveau F, et al. Modafinil restores memory performance and neural activity impaired by sleep deprivation in mice. 2007:55-63. PubMed PMID: 17698177.
21-McDermott CM, Hardy MN, Bazan NG, Magee JC. Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus. The Journal of physiology. 2006:553-65. PubMed PMID: 16322058. Pubmed Central PMCID: 1479879.
22-Khakpai F, Nasehi M, Zarrindast MR. The role of NMDA receptors of the medial septum and dorsal hippocampus on memory acquisition. Pharmacology, biochemistry, and behavior. 2016:18-25. PubMed PMID: 26780596.
23-Hosseini N, Nasehi M, Radahmadi M, Zarrindast MR. Effects of CA1 glutamatergic systems upon memory impairments in cholestatic rats. Behavioural brain research. 2013:636-45. PubMed PMID: 24050889.
24-Norozpour Y, Nasehi M, Sabouri-Khanghah V, Torabi-Nami M, Zarrindast MR. The effect of CA1 alpha2 adrenergic receptors on memory retention deficit induced by total sleep deprivation and the reversal of circadian rhythm in a rat model. Neurobiology of learning and memory. 2016:53-60. PubMed PMID: 27291858.
25-Nasehi M, Sahebgharani M, Haeri-Rohani A, Zarrindast MR. Effects of cannabinoids infused into the dorsal hippocampus upon memory formation in 3-days apomorphine-treated rats. Neurobiology of learning and memory. 2009:391-9. PubMed PMID: 19450698.
26-Najar F, Nasehi M, Haeri-Rohani SA, Zarrindast MR. The involvement of medial septum 5-HT1 and 5-HT2 receptors on ACPA-induced memory consolidation deficit: possible role of TRPC3, TRPC6 and TRPV2. Journal of psychopharmacology. 2015:1200-8. PubMed PMID: 26464456.
27-Nasehi M, Tabatabaie M, Khakpai F, Zarrindast MR. The effects of CA1 5HT4 receptors in MK801-induced amnesia and hyperlocomotion. Neuroscience letters. 2015:73-8. PubMed PMID: 25524640.
28-Nascimento DC, Andersen ML, Hipolide DC, Nobrega JN, Tufik S. Pain hypersensitivity induced by paradoxical sleep deprivation is not due to altered binding to brain mu-opioid receptors. Behavioural brain research. 2007:216-20. PubMed PMID: 17239968.
29-Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Seminars in neurology. 2005:117-29. PubMed PMID: 15798944.
30-Versace F, Cavallero C, De Min Tona G, Mozzato M, Stegagno L. Effects of sleep reduction on spatial attention. Biological psychology. 2006:248-55. PubMed PMID: 15978717.
31-Alhola P, Polo-Kantola P. Sleep deprivation: Impact on cognitive performance. Neuropsychiatric disease and treatment. 2007;3(5):553-67. PubMed PMID: 19300585. Pubmed Central PMCID: 2656292.
32-Bridoux A, Laloux C, Derambure P, Bordet R, Monaca Charley C. The acute inhibition of rapid eye movement sleep by citalopram may impair spatial learning and passive avoidance in mice. Journal of neural transmission. 2013:383-9. PubMed PMID: 23053350.
33-Alhaider IA, Aleisa AM, Tran TT, Alkadhi KA. Sleep deprivation prevents stimulation-induced increases of levels of P-CREB and BDNF: protection by caffeine. Molecular and cellular neurosciences. 2011:742-51. PubMed PMID: 21338685.
34-Copinschi G. Metabolic and endocrine effects of sleep deprivation. Essential psychopharmacology. 2005;6(6):341-7. PubMed PMID: 16459757.
35-Longordo F, Kopp C, Mishina M, Lujan R, Luthi A. NR2A at CA1 synapses is obligatory for the susceptibility of hippocampal plasticity to sleep loss. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009:9026-41. PubMed PMID: 19605640. Pubmed Central PMCID: 3849614.
36-Puig MV, Santana N, Celada P, Mengod G, Artigas F. In vivo excitation of GABA interneurons in the medial prefrontal cortex through 5-HT3 receptors. Cerebral cortex. 2004:1365-75. PubMed PMID: 15166106.
37-Turner TJ, Mokler DJ, Luebke JI. Calcium influx through presynaptic 5-HT3 receptors facilitates GABA release in the hippocampus: in vitro slice and synaptosome studies. Neuroscience. 2004;129(3):703-18. PubMed PMID: 15541891.
38-Amargos-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, et al. Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Cerebral cortex. 2004:281-99. PubMed PMID: 14754868.
39-Quinlan MG, Almey A, Caissie M, LaChappelle I, Radiotis G, Brake WG. Estradiol and striatal dopamine receptor antagonism influence memory system bias in the female rat. Neurobiology of learning and memory. 2013:221-9. PubMed PMID: 24036396.
40-Penalva RG, Lancel M, Flachskamm C, Reul JM, Holsboer F, Linthorst AC. Effect of sleep and sleep deprivation on serotonergic neurotransmission in the hippocampus: a combined in vivo microdialysis/EEG study in rats. The European journal of neuroscience. 2003:1896-906. PubMed PMID: 12752789.
41-Bjorvatn B, Gronli J, Hamre F, Sorensen E, Fiske E, Bjorkum AA, et al. Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat. Neuroscience. 2002;113(2):323-30. PubMed PMID: 12127089.
42-Kim EY, Mahmoud GS, Grover LM. REM sleep deprivation inhibits LTP in vivo in area CA1 of rat hippocampus. Neuroscience letters. 2005:163-7. PubMed PMID: 16039776.
43-Lopez-Rodriguez F, Wilson CL, Maidment NT, Poland RE, Engel J. Total sleep deprivation increases extracellular serotonin in the rat hippocampus. Neuroscience. 2003;121(2):523-30. PubMed PMID: 14522011.
44-Pehrson AL, Sanchez C. Serotonergic modulation of glutamate neurotransmission as a strategy for treating depression and cognitive dysfunction. CNS spectrums. 2014:121-33. PubMed PMID: 23903233. Pubmed Central PMCID: 3968911.
45-Gottlieb JP, Keller A. Intrinsic circuitry and physiological properties of pyramidal neurons in rat barrel cortex. Experimental brain research. 1997 Jun;115(1):47-60. PubMed PMID: 9224833.
46-Celada P, Puig MV, Artigas F. Serotonin modulation of cortical neurons and networks. Frontiers in integrative neuroscience. 2013;7-25. PubMed PMID: 23626526. Pubmed Central PMCID: 3630391.
47-Paxinos G., Watson,C., The  rat  brain in stereotaxic coordinates. ( 6th ed )2007, London, UK: Academic Press.