اثر ترانس سینامیک اسید بر اختلالات شناختی ناشی از تشنجات پریناتال در موشهای صحرایی

نویسندگان
مریم دلاویز 1
محمد امین عدالت منش 2
1 گروه زیست شناسی، دانشکده علوم، دانشگاه آزاد اسلامی، واحد شیراز، شیراز، ایران
2 گروه زیست شناسی، دانشکده علوم، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران
چکیده
مقدمه

تشنج پریناتال سبب آسیب جدی به سیستم عصبی جنین می­گردد که اختلالات شناختی و رفتاری را در نوزادان به همراه دارد. مطالعه حاضر به ارزیابی اثر ترانس­سینامیک اسید بر اختلالات شناختی و آسیب سلولی هیپوکامپ در مدل موش صحرایی تشنج پریناتال ناشی از پنتیلن­تترازول (PTZ) می­پردازد.

مواد و روش­ها

30 سر موش صحرایی ماده باردار به صورت تصادفی در 5 گروه کنترل، PTZ+NS، PTZ+SIN25، PTZ+SIN50 و PTZ+SIN100 تقسیم شدند. حیوانات با تجویز مکرر PTZ (40 میلی گرم بر کیلوگرم، درون صفاقی) از روز 13 بارداری به مدت 7 روز تیمار شدند. دو ساعت قبل از دریافت PTZ، موش­های صحرایی باردار با نرمال­سالین (گروه PTZ+NS) یا سینامیک اسید (گروه­های PTZ+NS با دوزهای 25، 50 و 100 میلی­گرم بر کیلوگرم) گاواژ شدند. ارزیابی حافظه کاری، یادگیری اجتنابی و رفتارهای شبه اضطرابی در نوزادان نر یک­ماهه صورت گرفت. سپس، نمونه­های مغز جهت مطالعه هیستوپاتولوژیک آسیب سلولی هیپوکامپ آنالیز شدند.

یافته­ها

کاهش معنی­دار در رفتار تناوبی (حافظه کاری)، تاخیر در ورود به محفظه تاریک (حافظه اجتنابی) و افزایش سطح اضطراب به همراه کاهش تراکم سلولی در نواحی مختلف هیپوکامپ در گروه PTZ+NS نسبت به گروه کنترل دیده شد (05/0˂p). در حالی که در گروه­های تیمار شده با سینامیک اسید، افزایش معنی­دار حافظه کاری، اجتنابی و تراکم سلولی هیپوکامپ نسبت به گروه PTZ+NS دیده شد (05/0˂p).

نتیجه­گیری

سینامیک اسید با کاهش آسیب سلولی هیپوکامپ سبب بهبود اختلالات شناختی در مدل تشنجات پریناتال ناشی از PTZدر موش های صحرایی می­شود.
کلیدواژه‌ها
سینامیک اسید
تشنج
دوران بارداری
هیپوکامپ
موش صحرایی

عنوان مقاله English

The effect of trans- Cinnamic acid on prenatal seizures induced cognitive deficits

نویسندگان English

Maryam Delaviz 1
Mohammad Amin Edalatmanesh 2
1 Deptartmet of Biology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran
2 Deptartmet of Biology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran
چکیده English

Introduction: Prenatal seizures cause serious damage in fetal nervous system leading to cognitive and behavioral deficits in newborns. This study examined the effect of trans-Cinnamic acid on cognitive impairment and hippocampal cell damage in rat model of Penthylentetrazole (PTZ)- induced prenatal seizure.

Material & Methods: 30 Pregnant Wistar rats were randomly divided in 5 groups: control, PTZ+NS, PTZ+SIN25, PTZ+SIN50 and PTZ+SIN100. Rats were treated by repeated injections of PTZ (40 mg/kg; i.p) on embryonic day (ED) 13 for 7 consecutive days. 2 hours before PTZ injection, pregnant rats were gavaged with normal saline (PTZ+NS) or Cinnamic acid (PTZ+SIN groups with 25, 50 and 100 mg/kg doses). The working memory, avoidance learning and anxiety like behaviors were evaluated in one month old male offspring. Then, brains were histopathologically analyzed for hippocampal cell damages.

Results: In comparison to controls, PTZ+NS group showed a significant decrease in alteration behavior (working memory), latency time to the dark room (avoidance memory) and increase level of anxiety with decrease of cell density in different areas of hippocampus (p˂ 0.05(. However, Cinnamic acid- treated groups showed a significant increase of working, avoidance memories and hippocampal cell density in comparison with PTZ+NS groups (p˂ 0.05(.

Conclusion: The Cinnamic acid with reduction of hippocampal cell damage was ameliorating cognitive deficits in rat model of prenatal seizures.

کلیدواژه‌ها English

Cinnamic acid
Seizures
Pregnancy
Hippocampus
rat
1. Samokhina E, Samokhin A. Neuropathological profile of the pentylenetetrazol (PTZ) kindling model. Int J Neurosci 2018;7:1-11.
2. Gunn BG, Baram TZ. Stress and Seizures: Space, Time and Hippocampal Circuits. Trends Neurosci 2017;40(11):667-79.
3. Walker MC. Pathophysiology of status epilepticus. Neurosci Lett 2018; 667:84-91.
4. Jia LJ, Wang WP, Li ZP, Zhen JL, An LW, Duan RS. Memantine attenuates the impairment of spatial learning and memory of pentylenetetrazol-kindled rats. Neurol Sci 2011; 32(4):609-13.
5. Jia P, Ewers JM, Zhao Z. Prioritization of epilepsy associated candidate genes by convergent analysis. PLoS One 2011; 6(2):e17162.
6. Singh KP, Verma N. Teratogenic potential of third-generation antiepileptic drugs: Current status and research needs. Pharmacol Rep 2019; 71(3):491-502.
7. Sveberg L, Svalheim S, Taubøll E. The impact of seizures on pregnancy and delivery. Seizure. 2015; 28:35-8.
8. Yerby MS. Special considerations for women with epilepsy. Pharmacotherapy. 2000; 20(8 Pt 2):159S-170S
9. Ferrari-Marinho T, Perucca P, Mok K, Olivier A, Hall J, Dubeau F, et al. Pathologic substrates of focal epilepsy influence the generation of high-frequency oscillations. Epilepsia 2015; 56(4):592-8.
10. Holmes GL, Harden C, Liporace J, Gordon J. Postnatal concerns in children born to women with epilepsy. Epilepsy Behav 2007; 11(3):270-6.
11. Bromley RL, Baker GA. Fetal antiepileptic drug exposure and cognitive outcomes. Seizure 2017; 44:225-31.
12. Koutroumanidou E, Kimbaris A, Kortsaris A, Bezirtzoglou E, Polissiou M, Charalabopoulos K, et al. Increased seizure latency and decreased severity of pentylenetetrazol-induced seizures in mice after essential oil administration. Epilepsy Res Treat 2013; 2013:532657.
13. Guzman JD. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity. Molecules. 2014; 19(12):19292-349.
14. Wilkins LR, Brautigan DL, Wu H, Yarmohammadi H, Kubicka E, Serbulea V, et al. Cinnamic Acid Derivatives Enhance the Efficacy of Transarterial Embolization in a Rat Model of Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 2017; 40(3):430-7.
15. Murakami Y, Kawata A, Suzuki S, Fujisawa S. Cytotoxicity and Pro-/Anti-inflammatory Properties of Cinnamates, Acrylates and Methacrylates Against RAW264.7 Cells. In Vivo 2018; 32(6):1309-22.
16. Szwajgier D, Borowiec K, Pustelniak K. The neuroprotective effects of phenolic acids: molecular mechanism of action. Nutrients 2017; 9(5):477.
17. Edalatmanesh M A, Amooei K. The lithium effect on learning and memory deficits and hippocampal level of BDNF in prenatal seizure kindled rats. J Fasa Univ Med Sci 2019; 8 (4):1088-96.
18. Haggag BS, Hasanin AM, Raafat MH, Abdel Kawy HS. Lamotrigine decreased hippocampal damage and improved vascular risk markers in a rat model of pentylenetetrazole induced kindling seizure. Korean J Physiol Pharmacol 2014;18: 269-78.
19. Bagha N, Edalatmanesh MA. Effectiveness of erythropoietin on working memory, passive avoidance learning and anxiety- like behaviors in prenatal food restriction model. Report of Health Care 2018; 4(1): 36- 43.
20. Edalatmanesh MA, Nikfarjam H, Moghadas M, Haddad-Mashadrizeh A, Robati R, Hashemzadeh MR. Histopathological and behavioral assessment of toxin-produced cerebellar lesion: a potent model for cell transplantation studies in the cerebellum. Cell J 2014;16(3):325-34.
21. Moghadas M, Edalatmanesh MA, Robati R. Histopathological Analysis from Gallic Acid Administration on Hippocampal Cell Density, Depression, and Anxiety Related Behaviors in A Trimethyltin Intoxication Model. Cell J 2016;17(4):659-67.
22. Naseer MI, Shupeng L, Kim MO. Maternal epileptic seizure induced by pentylenetetrazol: apoptotic neurodegeneration and decreased GABAB1 receptor expression in prenatal rat brain. Mol Brain 2009; 2:20.
23. Pourmotabbed A, Nedaei SE, Cheraghi M, Moradian S, Touhidi A, Aeinfar M, et al. Effect of prenatal pentylenetetrazol-induced kindling on learning and memory of male offspring. Neuroscience. 2011; 172:205-11.
24. Huang LT. Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms. Front Mol Neurosci 2014;7:8.
25. Zhen JL, Chang YN, Qu ZZ, Fu T, Liu JQ, Wang WP. Luteolin rescues pentylenetetrazole-induced cognitive impairment in epileptic rats by reducing oxidative stress and activating PKA/CREB/BDNF signaling. Epilepsy Behav 2016;57(Pt A):177-84.
26. Naseer MI, Lee HY, Ullah N, Ullah I, Park MS, Kim SH, et al. Ethanol and PTZ effects on siRNA-mediated GABAB1 receptor: down regulation of intracellular signaling pathway in prenatal rat cortical and hippocampal neurons. Synapse 2010; 64(3):181-90.
27. Parisi P, Francia A, Vanacore N, Fiore S, Giallonardo AT, Manfredi M. Psychomotor development and general movements in offspring of women with epilepsy and anticonvulsant therapy. Early Hum Dev 2003; 74(2):97-108.
28. Kantola-Sorsa E, Gaily E, Isoaho M, Korkman M. Neuropsychological outcomes in children of mothers with epilepsy. J Int Neuropsychol Soc 2007; 13(4):642-52.
29. Rajabzadeh AA, Bideskan AR, Haghir H, Fazel AR. Morphometrical study of polysialylated neural cell adhesion molecule positive cells in rat pups hippocampus following induction of seizure during pregnancy. Iran Biomed J 2011; 15(4):157-63.
30. Szyndler J, Maciejak P, Kołosowska K, Chmielewska N, Skórzewska A, Daszczuk P, Płaźnik A. Altered expression of GABA-A receptor subunits in the hippocampus of PTZ-kindled rats. Pharmacol Rep 2018; 70(1):14-21.
31. Siddiqui AH, Joseph SA. CA3 axonal sprouting in kainate-induced chronic epilepsy. Brain Res 2005; 1066:129–46.
32. Parent JM, Elliott RC, Pleasure SJ, Barbaro NM, Lowenstein DH. Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Ann Neurol 2006; 59:81–91.
33. Lagae L. The importance of assessing behaviour and cognition in antiepileptic drug trials in children and adolescents. Acta Neurol Belg 2017;117(2):425-32.
34. Inoyama K, Meador KJ. Cognitive outcomes of prenatal antiepileptic drug exposure. Epilepsy Res 2015; 114:89-97.
35. Najafi MR, Bazooyar B, Zare M, Aghaghazvini MR, Ansari B, Rajaei A, Dashti M. The Investigation of Insulin Resistance in Two Groups of Epileptic Patients Treated with Sodium Valproate and Carbamazepine. Adv Biomed Res 2017; 6:25.
36. Lu Y, Wang X, Feng J, Xie T, Si P, Wang W. Neuroprotective effect of astaxanthin on newborn rats exposed to prenatal maternal seizures. Brain Res Bull 2019; 148:63-69.
37. Mehla J, Reeta KH, Gupta P, Gupta YK. Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model. Life Sci 2010; 87(19-22):596-603.
38. Ghaderkhani S, Moloudi MR, Izadpanah E, Mohammadi R, Rostami A, Khom P, Hassanzadeh K. Effect of hydroalcoholic extract of cinnamomum on strychnine-induced seizure in mice. Journal of Isfahan Medical School 2014; 32(299):1388-95.
39. Edalatmanesh M A, Khodabandeh H, Yazdani N, Rafiei S. Effect of Cinnamomum Zeylanicum Extract on Memory and Hippocampal Cell Density in Animal Model of Diabetes. J Arak Uni Med Sci. 2018; 21(6):56-66.
40. Anlar HG, Bacanlı M, Çal T, Aydın S, Ar N, Ündeğer Bucurgat Ü, et al. Effects of cinnamic acid on complications of diabetes. Turk J Med Sci 2018; 48(1):168-77.
مجله دانشگاه علوم پزشکی نیشابور
دوره 7، شماره 3 - شماره پیاپی 24
تابستان 1398
صفحه 104-118