Sesamin alleviates defects in seizure, behavioral symptoms, and hippocampus electroencephalogram in a pentylenetetrazol rat model

Document Type : Original Article

Authors

Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Objective(s): Seizure is a prevalent disorder reflected by powerful and sudden activity of neural networks in the brain that leads to tonic-clonic attacks. These signs may be due to an increase in excitatory/inhibitory neurotransmitters ratio. So, the current experiment aimed to examine the seizure and neurobehavioral parameters, as well as the hippocampus local electroencephalogram (EEG) after seizure with and without sesamin pretreatment.   
Materials and Methods: Sesamin (15, 30, and 60 mg/kg/5 ml, intraperitoneal or IP, vehicle: dimethyl sulfoxide or DMSO, for 3 days) was administrated before pentylenetetrazol (PTZ) (60 mg/kg/10 ml, IP, vehicle: saline), which induces acute seizure in adult male Wistar rats (230 ± 20 g, six weeks old). Different phases of seizures (score, latency, duration, and frequency), behavioral parameters (passive avoidance memory, anxiety, and locomotor activity), and hippocampus local EEG were evaluated after the injections. At the end of the experiments, oxidative stress markers plus gene expression of phosphoinositide 3-kinase/protein kinase B or PI3K/Akt mRNA were measured in the hippocampus.  
Results: Pretreatment with sesamin (30 mg/kg) could significantly decrease seizure scores and oxidative stress in the hippocampus. PTZ injection induced EEG deficits and neurobehavioral impairments which were significantly decreased by sesamin, especially in Beta, Theta, and delta EEG waves.  Also, the expression of PI3K/Akt significantly increased in the sesamin (30 mg/kg) group in comparison with the PTZ group. 
Conclusion: Sesamin could prevent seizure attacks and neurobehavioral and EEG deficits induced by pentylenetetrazol, probably through the PI3K/Akt signaling pathway.

Keywords

Main Subjects


1. Rodrigues AD, Scheffel TB, Scola G, Santos MT, Fank B, de Freitas SC, et al. Neuroprotective and anticonvulsant effects of organic and conventional purple grape juices on seizures in Wistar rats induced by pentylenetetrazole. Neurochem Int 2012; 60:799-805.
2. Elger CE, Hoppe C. Diagnostic challenges in epilepsy: Seizure under-reporting and seizure detection. Lancet Neurol 2018; 17:279-288.
3. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging in Aging 2018 13:757-772.
4. Jin M, Zhang B, Sun Y, Zhang S, Li X, Sik A, et al. Involvement of peroxisome proliferator-activated receptor γ in anticonvulsant activity of α-asaronol against pentylenetetrazole-induced seizures in zebrafish. Neuropharmacology 2020; 162:107760.
5. Jetté N, Sander JW, Keezer MR. Surgical treatment for epilepsy: The potential gap between evidence and practice. Lancet Neurol 2016; 15:982-994.
6. Zalkhani R, Moazedi A, Najafzadehvarzi H. Investigating the effects of subchronic sesame and flaxseed oils consumption against seizure and depression in adult male mice. Iran J Pharm Res 2020; 16:73-80.
7. Puttachary S, Sharma S, Stark S, Thippeswamy T. Seizure-induced oxidative stress in temporal lobe epilepsy. Biomed Res Int 2015; 2015.
8. Salim S. Estresse oxidativo eo sistema nervoso central. J Pharmacol Exp Ther 2017; 360:201-205.
9. Fan D, Yang Z, Liu F-y, Jin Y-G, Zhang N, Ni J, et al. Sesamin protects against cardiac remodeling via Sirt3/ROS pathway. Cell Physiol Biochem 2017; 44:2212-2227.
10. Zalkhani R, Najafzadehvarzi H, Moazedi A. The effect of acute and chronic sesame oil consumption on the strychnine induced seizure in adult rats. J Ardebil Univ Med Sci 2019; 18:470-478.
11. Mirshekari Jahangiri H, Sarkaki A, Farbood Y, Dianat M, Goudarzi G. Gallic acid affects blood-brain barrier permeability, behaviors, hippocampus local EEG, and brain oxidative stress in ischemic rats exposed to dusty particulate matter. Environ Sci Pollut Res Int 2020; 27:5281-5292.
12. Babri S, Amani M, Mohaddes G, Mirzaei F, Mahmoudi F. Effects of intrahippocampal injection of ghrelin on spatial memory in PTZ-induced seizures in male rats. Neuropeptides 2013; 47:355-360.
13. Kola PK, Akula A, NissankaraRao LS, Danduga RCSR. Protective effect of naringin on pentylenetetrazole (PTZ)-induced kindling; possible mechanisms of antikindling, memory improvement, and neuroprotection. Epilepsy Behav 2017; 75:114-126.
14. Eastman CL, D’Ambrosio R, Ganesh T. Modulating neuroinflammation and oxidative stress to prevent epilepsy and improve outcomes after traumatic brain injury. Neuropharmacology 2020; 172:1-30
15. Paltian JJ, Dos Reis AS, de Oliveira RL, da Fonseca CA, Domingues WB, Dellagostin EN, et al. The anxiolytic effect of a promising quinoline containing selenium with the contribution of the serotonergic and GABAergic pathways: modulation of parameters associated with anxiety in mice. Behav Brain Res 2020; 393:112797.
16. Sutula TP, Dudek FE. Unmasking recurrent excitation generated by mossy fiber sprouting in the epileptic dentate gyrus: an emergent property of a complex system. Prog Brain Res 2007; 163:541-563.
17. Adeli H, Ghosh-Dastidar S, Dadmehr N. A wavelet-chaos methodology for analysis of EEGs and EEG subbands to detect seizure and epilepsy. IEEE Trans Biomed Eng 2007; 54:205-211.
18. Sikdar D, Roy R, Mahadevappa M. Epilepsy and seizure characterisation by multifractal analysis of EEG subbands. Biomed Signal Process Control 2018; 41:264-270.
19. Xue Y, Xie N, Cao L, Zhao X, Jiang H, Chi Z. Diazoxide preconditioning against seizure-induced oxidative injury is via the PI3K/Akt pathway in epileptic rat. Neurosci lett 2011; 495:130-134.
20. Wei H, Duan G, He J, Meng Q, Liu Y, Chen W, et al. Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K/Akt/GSK‑3β signaling pathway. Exp Ther Med 2018; 15:1136-1142.
21. Xu Z-P, Li L, Bao J, Wang Z-H, Zeng J, Liu E-J, et al. Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer’s model. PloS One 2014; 9:1-11
22. Han T, Qin Y, Mou C, Wang M, Jiang M, Liu B. Seizure induced synaptic plasticity alteration in hippocampus is mediated by IL-1β receptor through PI3K/Akt pathway. Am J Transl Res 2016; 8: 4499-4509
23. Abeer A. Khedr MFSE-D, Hebe Ezz El- Din Yossef. The protective role of pomegranate (Punicagranatum L.) juice against hepatotoxicity induced bypentylenetetrazol in epileptic rats. Life Sci J 2015; 12:119-124.
24. Hsieh PF, Hou C-W, Yao P-W, Wu S-P, Peng Y-F, Shen M-L, et al. Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation. J Neuroinflammation 2011; 8:1-10.
25. Homayoun H, Khavandgar S, Dehpour AR. Anticonvulsant effects of cyclosporin A on pentylenetetrazole-induced seizure and kindling: modulation by nitricoxidergic system. Brain Res 2002; 939:1-10.
26. Sarkaki A, Rezaiei M, Rafieirad M. Improving active and passive avoidance memories deficits due to permanent cerebral ischemia by pomegranate seed extract in female rats. Malays J Med Sci 2013; 20: 25-34
27. Mansouri MT, Soltani M, Naghizadeh B, Farbood Y, Mashak A, Sarkaki A. A possible mechanism for the anxiolytic-like effect of gallic acid in the rat elevated plus maze. Pharmacol Biochem Behav 2014; 117:40-46.
28. Mansouri MT, Farbood Y, Naghizadeh B, Shabani S, Mirshekar MA, Sarkaki A. Beneficial effects of ellagic acid against animal models of scopolamine-and diazepam-induced cognitive impairments. Pharm Biol 2016; 54:1947-1953.
29. Liu C-M, Zheng G-H, Ming Q-L, Chao C, Sun J-M. Sesamin protects mouse liver against nickel-induced oxidative DNA damage and apoptosis by the PI3K-Akt pathway. J Agric Food Chem 2013; 61:1146-1154.
30. Sarkaki A, Farbood Y, Dolatshahi M, Mansouri SMT, Khodadadi A. Neuroprotective effects of ellagic acid in a rat model of Parkinson’s disease. Acta Med Iran 2016:494-502.
31. Liu Y, Wang H, Liu N, Du J, Lan X, Qi X, et al. Oxymatrine protects neonatal rat against hypoxic-ischemic brain damage via PI3K/Akt/GSK3β pathway. Life Sci 2020; 254:116444.
32.Ciumas C, Wahlin TR, Jucaite A, Lindstrom P, Halldin C, Savic I. Reduced dopamine transporter binding in patients with juvenile myoclonic epilepsy. Neurology 2008; 71:788-794.
33. Naveen Sharma GS, 1Megha Jain,AK Jain,Ashish Mangal. Evaluation of anti epileptic activity of sesamum indicum leaves extract in mice. World J Pharm Res 2014; 4:1595-1604.
34. Advani U, Ansari A, Menghani E. Anticonvulsant potentials of Sesamum indicum and Allium sativum oil alone and in combination in animal models. Int J Pharm Pharm Sci 2011; 3:154-158.
35. Kuo P-C, Kao Z-H, Lee S-W, Wu S-N. Effects of sesamin, the major furofuran lignan of sesame oil, on the amplitude and gating of voltage-gated Na+ and K+ currents. Molecules 2020; 25:1-19
36. Hassanzadeh P, Arbabi E, Rostami F. The ameliorative effects of sesamol against seizures, cognitive impairment and oxidative stress in the experimental model of epilepsy. Iran J Basic Med Sci 2014; 17:100-107.
37. Hou RCW, Huang HM, Tzen JT, Jeng KCG. Protective effects of sesamin and sesamolin on hypoxic neuronal and PC12 cells. J Neurosci Res 2003; 74:123-133.
38. Farrell JS, Colangeli R, Wolff MD, Wall AK, Phillips TJ, George A, et al. Postictal hypoperfusion/hypoxia provides the foundation for a unified theory of seizure‐induced brain abnormalities and behavioral dysfunction. Epilepsia 2017; 58:1493-1501.
39. Khan MM, Ishrat T, Ahmad A, Hoda MN, Khan MB, Khuwaja G, et al. Sesamin attenuates behavioral, biochemical and histological alterations induced by reversible middle cerebral artery occlusion in the rats. Chem Biol Interact 2010; 183:255-263.
40. Ahmad S, Khan MB, Hoda MN, Bhatia K, Haque R, Fazili IS, et al. Neuroprotective effect of sesame seed oil in 6-hydroxydopamine induced neurotoxicity in mice model: cellular, biochemical and neurochemical evidence. Neurochem Res 2012; 37:516-526.
41. Farbood Y, Ghaderi S, Rashno M, Khoshnam SE, Khorsandi L, Sarkaki A, et al. Sesamin: a promising protective agent against diabetes-associated cognitive decline in rats. Life sci 2019; 230:169-177.
42. Bournival J, Francoeur M-A, Renaud J, Martinoli M-G. Quercetin and sesamin protect neuronal PC12 cells from high-glucose-induced oxidation, nitrosative stress, and apoptosis. Rejuvenation res 2012; 15:322-333.
43. VanGilder R, Kelly K, Chua M, Ptachcinski R, Huber JD. Administration of sesamol improved blood–brain barrier function in streptozotocin-induced diabetic rats. Exp brain res 2009; 197:23-34.
44.Ahmad S, Yousuf S, Ishrat T, Khan MB, Bhatia K, Fazli IS, et al. Effect of dietary sesame oil as antioxidant on brain hippocampus of rat in focal cerebral ischemia. Life Sci 2006; 79:1921-1928.
45. Ahmad S, ElSherbiny NM, Jamal MS, Alzahrani FA, Haque R, Khan R, et al. Anti-inflammatory role of sesamin in STZ induced mice model of diabetic retinopathy. J Neuroimmun 2016; 295:47-53.
46. Gupta A, Singh P, Karlekar M. A novel signal modeling approach for classification of seizure and seizure-free EEG signals. IEEE Trans Neural Syst Rehabil Eng 2018; 26:925-935.
47. Spera V, Sitnikova T, Ward MJ, Farzam P, Hughes J, Gazecki S, et al. Pilot study on dose-dependent effects of transcranial photobiomodulation on brain electrical oscillations: A potential therapeutic target in Alzheimer’s disease. J Alzheimers Dis 2021; 83:1481-1498.
48. Jeng K, Hou R. Sesamin and sesamolin: nature’s therapeutic lignans. Curr Enzym Inhib 2005; 1:11-20.
49.Van Erum J, Van Dam D, De Deyn PP. PTZ-induced seizures in mice require a revised Racine scale. Epilepsy Behav 2019; 95:51-55.
50. Nazıroğlu M, Kutluhan S, Yılmaz M. Selenium and topiramate modulates brain microsomal oxidative stress values, Ca 2+-ATPase activity, and EEG records in pentylentetrazol-induced seizures in rats. J Membr Biol 2008; 225:39-49.
51. Meador KJ. The basic science of memory as it applies to epilepsy. Epilepsia 2007; 48:23-25.
52.Adeli H, Zhou Z, Dadmehr N. Investigation of EEG records in an epileptic tolerant utilizing wavelet change. J Neurosci Methods 2003; 123:69-87.
53. Kannathal N, Choo M. UR Achar. PK Sadasivana Entropies for detection of epilepsy in EEG Comput Methods Programs Biomed 2005; 80:187-194.
54. Kullmann D, Asztely F, Walker M. The role of mammalian ionotropic receptors in synaptic plasticity: LTP, LTD and epilepsy. Cell MoL Life Sci 2000; 57:1551-1561.
55. Omrani A, Fathollahi Y, Almasi M, Semnanian S, Mohammad S, Firoozabadi P. Contribution of ionotropic glutamate receptors and voltage-dependent calcium channels to the potentiation phenomenon induced by transient pentylenetetrazol in the CA1 region of rat hippocampal slices. Brain Res 2003; 959:173-181.
56. Xue Y, Xie N, Lin Y, Xu J, Han Y, Wang S, et al. Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures. Brain res 2011; 1383:135-140.
57. Liu A-H, Chu M, Wang Y-P. Up-regulation of Trem2 inhibits hippocampal neuronal apoptosis and alleviates oxidative stress in epilepsy via the PI3K/Akt pathway in mice. Neurosci Bull 2019; 35:471-485.
58. Vieira ÉLM, Martins FMA, Bellozi PMQ, Gonçalves AP, Siqueira JM, Gianetti A, et al. PI3K, mTOR and GSK3 modulate cytokines’ production in peripheral leukocyte in temporal lobe epilepsy. Neurosci Lett 2021; 756:1-9
59. Hu F, Shao L, Zhang J, Zhang H, Wen A, Zhang P. Knockdown of ZFAS1 inhibits hippocampal neurons apoptosis and autophagy by activating the PI3K/AKT pathway via up-regulating miR-421 in epilepsy. Neurochem Res 2020; 45:2433-2441.
60. Huang J-B, Hsu S-P, Pan H-Y, Chen S-D, Chen S-F, Lin T-K, et al. Peroxisome proliferator-activated receptor γ coactivator 1α activates vascular endothelial growth factor that protects against neuronal cell death following status epilepticus through PI3K/AKT and MEK/ERK signaling. Int J Cell Sci Mol Biol 2020; 21:7247.
61. Zhang H, Tao J, Zhang S, Lv X. LncRNA MEG3 reduces hippocampal neuron apoptosis via the PI3K/AKT/mTOR pathway in a rat model of temporal lobe epilepsy. Neuropsychiatr Dis Treat 2020:2519-2528.
62. Han X, Zhou N, Hu H, Li X, Liu H. Nicotine Alleviates Cortical Neuronal Injury by Suppressing Neuroinflammation and Upregulating Neuronal PI3K-AKT Signaling in an Eclampsia-Like Seizure Model. Neurotox Res 2020; 38:665-681.
63. Xiao Z, Peng J, Yang L, Kong H, Yin F. Interleukin-1β plays a role in the pathogenesis of mesial temporal lobe epilepsy through the PI3K/Akt/mTOR signaling pathway in hippocampal neurons. J Neuroimmunol 2015; 282:110-117.