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Effects of Boswellia serrata resin on central nervous system: a mini review 2 2 Medicinal plants are used for different purposes in traditional medicine. Boswellia serrata (B. serrata) from Burseracea family has been widely used for human medical purposes. This plant known as frankincense or olibanum has a resin with therapeutic properties. The main constituent of this resin is boswellic acid that plays an important role in various fields. From past to present, many studies had been shown that olibanum and its main constituent, boswellic acid, have antiinflammatory, antioxidant, antitumor, anti-arthritic, antimicrobial and anti-carcinogenic effects. In addition, many findings about effects of B. serrata and its ingredients on central nervous system (CNS) are available. Therefore, the aim of this study is to review in vivo and in vitro evidence attributed to this plant and its constituents on CNS. Databases including Web of Sciences, Scopus, PubMed and Google Scholar were explored for entries from the beginning of January 2000 until the end of November 2020. Findings reveal that B. serrata and its constituents have neuroprtotective effects and ameliorate learning and memory malfunction. These effects mainly are attributed to the antioxidant and anti-inflammatory properties of this plant. 288 295 2021/01/12 1399/10/23 2021/02/8 1399/11/20 Narges Marefati Narges Marefati Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Iran Safoura Khamse Safoura Khamse Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Iran Somaieh Mansouri Somaieh Mansouri Department of Anatomy, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran Iran Mahmoud Hosseini Mahmoud Hosseini Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Iran Akbar Anaeigoudari Akbar Anaeigoudari Department of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran Iran Anaeia@jmu.ac.ir Boswellia serrata Frankincense Olibanum Central nervous system Abdel-tawab M, Werz O, Schubert-zsilavecz M. Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Clin Pharmacokinet 2011; 50: 349-69. doi: 10.2165/11586800-000000000-00000 ##Adake P, Petimani MS, Jayaraj M, Rao S. Preclinical evaluation of Boswellia serrata for anxiolytic activity. Int J Basic Clin 2015; 4: 551-555. doi: 10.18203/2319-2003.ijbcp20150038##Beghelli D, Isani G, Roncada P, Andreani G, Bistoni O, et al. Antioxidant and ex vivo immune system regulatory properties of Boswellia serrata extracts. Oxid Med Cell Longev 2017; 7468064. https://doi.org/10.1155/2017/7468064##Beheshti S, Aghaie R. Therapeutic effect of frankincense in a rat model of Alzheimer’s disease. Avicenna J Phytomed 2016; 4: 468-75.##Beheshti S, Skakakomi AG, Ghaedi K, Dehestani H. Frankincense upregulates the hippocampal calcium/calmodulin kinase II-α during development of the rat brain and improves memory performance. Int J Dev Neurosci 2018; 69: 44-48. doi: 10.1016/j.ijdevneu.2018.06.011.##Brookmeyer R, Johnson E, Ziegler-graham, K, Arrighi, HM. Forecasting the global burden of Alzheimer’s disease. Alzheimers dement 2007; 3: 186-191. doi: 10.1016/j.jalz.2007.04.381##Ding Y, Chen M, Wang M, Wang M, Zhang T, Park J, et al. Neuroprotection by acetyl-11-keto-β-boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway. Sci Rep 2014; 4: 1-9. doi: 10.1038/srep07002##Doaee P, Rajaei Z, Roghani M, Alaei H, Kamalinejad M. Effects of Boswellia serrata resin extract on motor dysfunction and brain oxidative stress in an experimental model of Parkinson’s disease. Avicenna J Phytomed 2019; 3: 281-290.##Ebrahimpour S, Fazeli M, Mehri S, Taherianfard M, Hosseinzadeh H. Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity:-Neuroprotective effect of Boswellic acid. J pharmacopuncture 2017; 1: 10-17. doi: 10.3831/KPI.2017.20.001##Forouzanfar F, Hosseinzadeh H, Ebrahimzadeh Bideskan A, Sadeghnia HR. Aqueous and ethanolic extracts of Boswellia serrata protect against focal cerebral ischemia and reperfusion injury in rats. Phytother Res 2016; 12: 1954-1967. doi: 10.1002/ptr.5701##Gomaa AA, Makboul RM, Al-Mokhtar MA, Nicola MA. Polyphenol-rich Boswellia serrata gum prevents cognitive impairment and insulin resistance of diabetic rats through inhibition of GSK3beta activity, oxidative stress and pro-inflammatory cytokines. Biomed Pharmacother 2019; 109: 281-292. doi: 10.1016/j.biopha.2018.10.056 ##Hosseini-Sharifabad M, Esfandiari E. Effect of Boswellia serrata gum resin on the morphology of hippocampal CA1 pyramidal cells in aged rat. Anat Sci Int 2015a; 1: 47-53. doi: 10.1007/s12565-014-0228-z ##Hosseini-Sharifabad M, Esfandiari E. Effect of Boswellia serrata gum resin on the morphology of hippocampal CA1 pyramidal cells in aged rat. Anat Sci Int 2015b; 1: 47-53. doi: 10.1007/s12565-014-0228-z##Hosseini M, Hadjzadeh MAR, Derakhshan M, Havakhah S, Rassouli FB, Rakhshandeh H, et al. The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze. Arch Pharm Res 2010; 3: 463-468. doi: 10.1007/s12272-010-0317-z##Jalili C, Salahshoor M, Pourmotabbed A, Moradi S, Roshankhah S, Darehdori AS, et al. The effects of aqueous extract of Boswellia Serrata on hippocampal region CA1 and learning deficit in kindled rats. Res Pharm Sci 2014; 5, 351-8.##Jebelli A, Khalaj-Kondori M, Bonyadi M, Feizi MAH, Rahmati-Yamchi M. Beta-boswellic acid and ethanolic extract of olibanum regulating the expression levels of CREB-1 and CREB-2 genes. Iran J Pharm Res 2019; 2: 877-877. doi: 10.22037/ijpr.2019.1100665##Kasali AA, Adio AM, Oyedeji AO, Eshilokun AO, Adefenwa M. Volatile constituents of Boswellia serrata Roxb.(Burseraceae) bark. Flavour Fragr J 2002; 17: 462-464. https://doi.org/10.1002/ffj.1124|##Kazmi S, Kafami L, Ebrahimi A, Jameie B, Joghataiee MT. The effects of boswellia resin extract on dopaminergic cell line, SK-N-SH, against MPP+-induced neurotoxicity. Basi Clin Neurosci 2011; 3: 16-21.##Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee–a randomized double blind placebo controlled trial. Phytomedicine 2003; 1: 3-7. doi: 10.1078/094471103321648593##Krieglstein CF, Anthoni C, Rijcken EJ, Laukötter M, Spiegel HU, Boden SE, et al. Acetyl-11-keto-β-boswellic acid, a constituent of a herbal medicie from Boswellia serrata resin, attenuates experimental ileitis. Int J Colorectal Dis 2001; 2: 88-95. doi: 10.1007/s003840100292 ##Kunnumakkara AB, Nair AS, Sung B, Pandey MK, Aggarwal BB. Boswellic Acid Blocks Signal Transducers and Activators of Transcription 3 Signaling, Proliferation, and Survival of Multiple Myeloma via the Protein Tyrosine Phosphatase SHP-1. Mol Cancer Res 2009; 1:118-28. doi: 10.1158/1541-7786.MCR-08-0154.##Lampl C, Haider B, Schweiger C. Long-term efficacy of Boswellia serrata in four patients with chronic cluster headache. Cephalalgia 2012; 32: 719-722. doi: 10.1177/0333102412451357##Lu CW, Lin TY, Wang SJ. 11-Keto-beta-Boswellic Acid Attenuates Glutamate Release and Kainic Acid-Induced Excitotoxicity in the Rat Hippocampus. Planta Med 202; 6: 434-441. doi: 10.1055/a-1107-9337. Epub 2020 Feb 25 ##Mahboubi M, Taghizadeh M, Talaei S. A, Firozeh SMT, Rashidi AA, Tamtaji OR. Combined Administration of Melissa officinalis and Boswellia serrata Extracts in an Animal Model of Memory. Iran J Psychiatry Behav Sci 2016; 3: e681. doi: 10.17795/ijpbs-681##Marefati N, Beheshti F, Memarpour S, Bayat R, Shafei MN, Sadeghnia HR, et al. The effects of acetyl-11-keto-β-boswellic acid on brain cytokines and memory impairment induced by lipopolysaccharide in rats. Cytokine, 2020; 131: 155107. doi: 10.1016/j.cyto.2020.155107##Mohamed TM, Youssef MAM, Bakry AA. El-Keiy MM. 2020. Alzheimer’s disease improved through the activity of mitochondrial chain complexes and their gene expression in rats by boswellic acid. Metab Brain Dis 2020; doi: 10.1007/s11011-020-00639-7##Moussaieff A, Mechoulam R. Boswellia resin: from religious ceremonies to medical uses; a review of in‐vitro, in‐vivo and clinical trials. J Pharm Pharmacol, 2009; 10: 1281-1293. doi: 10.1211/jpp/61.10.0003##Moussaieff A, Rimmerman N, Bregman T, Straiker A, Felder CC, Shoham S, et al. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain. FASEB J 2008; 22: 3024-3034. doi: 10.1096/fj.07-101865 ##Rajabian A, Sadeghnia H, Fanoudi S, Hosseini A. Genus Boswellia as a new candidate for neurodegenerative disorders. 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Association of two specific haplotypes of serotonin transporter gene with fluvoxamine treatment outcomein Iranian patients with obsessive compulsive disorder 2 2 Introduction: Converging lines of evidence indicate that serotonin transporter has a role in response to selective serotonin reuptake inhibitors pharmacotherapy in a variety of neuropsychiatric disorders. In the present study, the association of four functional loci of the serotonin transporter gene (SLC6A4) with fluvoxamine treatment outcome in Iranian patients with obsessive compulsive disorder (OCD) has been investigated. Methods: A total of 352 Iranian OCD patients were screened for the treatment outcome. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150-300mg). Finally, 132 patients who had completed their treatment were assigned to three groups (responders, non-responders and refractory) and underwent genotyping for SLC6A4 variations (STin2, 5-HTTLPR, rs25531 and rs25532) employing PCR-RFLP. Results: Results showed no significant differences between different STin2, 5-HTTLPR/rs25531 and rs25532 single locus genotype frequencies. However, significant associations of two SLC6A4 haplotypes with treatment response were detected. Conclusion: Detected association of two SLC6A4 haplotypes with response to fluvoxamine in OCD patients proposed that the research emphasis of OCD pharmacogenetic studies may be placed on haplotype association analyses in candidate genes. This may represent a significant advance over single-locus investigations as a way to understand the influence of genetic factors on drug response in OCD. 296 305 2021/01/122020/10/10 1399/7/19 2021/02/82021/02/8 1399/11/20 Sareh Asadi Sareh Asadi Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran s.asadi@sbmu.ac.ir Fatemeh Sadat Rashidi Fatemeh Sadat Rashidi Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Jamal Shams Jamal Shams Behavioral Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran Iran Abolhassan Ahmadiani Abolhassan Ahmadiani Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran SLC6A4 5-HTTLPR rs25531 rs25532 STin2 Association A P. Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub, 2013.##Biernacka J M, McElroy S L, Crow S, Sharp A, Benitez J, Veldic M, et al. 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High- and moderate-intensity training are equipotent in abrogating myocardial inflammation in rats fed aWestern diet 2 2 Introduction: Western diet (WD) activates inflammatory pathways in the myocardium, where jeopardizes contractile function. This study aimed to compare the anti-inflammatory effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) in rats fed a WD. Methods: Wistar rats were assigned to the six groups: normal diet (ND)+HIIT, WD+HIIT, ND+MICT, WD+MICT, sedentary fed a ND or WD (SED+ND and SED+WD, respectively). HIIT and MICT were performed on a motorized treadmill, five consecutive days/week for 12 weeks. In these animals, visceral fat mass and myocardial expression of pro-inflammatory cytokines i.e. tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) were measured. Western blotting was performed to identify cardiac protein expression. Results: WD+SED significantly increased visceral fat mass compared with ND+SED. WD+SED significantly resulted in TNF-α over-expression compared with ND+SED. There were no significant differences in MPO expression between WD+SED and ND+SED. In trained groups, visceral fat mass and TNF-α expression were lower in WD+HIIT and WD+MICT compared with WD+SED, with similar effects between HIIT and MICT modes. MPO expression was significantly lower in ND+HIIT and ND+MICT compared with ND+SED, with similar effects between HIIT and MICT modes. Conclusion: WD co-existing with SED paves the way to a pro-inflammatory milieu in the heart. 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The behavioral and molecular effects of estradiol and progesterone on a rat model of spinothalamic tract lesion 2 2 Introduction: The spinal cord injury is temporary or permanent damage in the spinal cord that disturbs the motor and sensory functions. The neuroprotective effects of steroids has been reported previously. Therefore, we designed a study to investigate the effects of different doses of estradiol (Est) and progesterone (Prog) on unilateral lesion of the spinothalamic tract (STT). Methods: The 77 male adult Wistar rats were under the anesthesia for dorsal laminectomy at the spinal segments T8–T9. A tungsten-electrode was targeted to the right STT and unilateral lesion was made by a brief current pulse (300μA, 90s). Rats were divided into 11 groups and Est or Prog (2, 4, 8 and 16mg/kg) were administered 30min post-injury. Mechanical allodynia and open field as assessed before, 14 and 28 days after the injection then the animals were sacrificed. The western blotting was performed on T8–9 spinal segments to evaluate protein expression of ERK, p-P38, JNK, Iba1 and GFAP at the lesion site. Results: Est but not Prog significantly increased the pain threshold and motor activity at the dose of 8mg/kg on post-surgery days 14 and 28. Est but not Prog significantly increased the protein expression of ERK while decreased JNK protein. Both Est and Prog significantly decreased protein expression of p-P38, Iba1 and GFAP. Conclusion: These results show Est (8mg/kg) is able to decrease mechanical allodynia and improve motor activity 14 and 28 days after spinothalamic tract lesion. It seems ERK, p-P38, JNK, Iba1 and GFAP are involved. 314 327 2021/01/122020/10/102020/12/312020/08/11 1399/5/21 2021/02/82021/02/82021/02/12021/04/6 1400/1/17 Abbas Alimoradian Abbas Alimoradian Department of Pharmacology, School of Medicine, Arak University of Medical Sciences, Arak, Iran Iran Fatemeh Abbaszadeh Fatemeh Abbaszadeh Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Masoumeh Jorjani Masoumeh Jorjani Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran msjorjani@sbmu.ac.ir Mehdi Sadegh Mehdi Sadegh Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran Iran Estradiol Progesterone Spinal cord injury Neuropathic pain Molecular Signaling Bonin RP, Bories C, De Koninck Y. A simplified up-down method (sudo) for measuring mechanical nociception in rodents using von frey filaments. 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Antidepressant efficacy of MLC901 in the 6-hydroxydopamine mice model of Parkinson’s disease 2 2 Introduction: Depression is a common mood disorder in patients with Parkinson’s disease (PD), which negatively influences the quality of life and enhances caregiver burden. MLC901, a traditional medicine, has been demonstrated to be useful in preclinical and clinical studies. The aim was to study the effect of MLC901 on depression behavior in a mouse model of PD, comprising in the unilateral striatal delivery of the neurotoxin 6-hydroxydopamine (6-OHDA). Methods: Female NMRI mice were divided into the following groups: sham/saline group, 6-OHDA/saline group, sham/MLC901 (40μg/kg) group and 6-OHDA/MLC901 group. Intraperitoneal treatments of MLC901 were started one week after the stereotaxic surgery that continued for 4 weeks (5 days/week). Locomotion was monitored using an openfield test and depressive-like responses were measured by forced swim test (FST) and tail suspension test (TST). Results: We found that MLC901 prevented the increased immobility time in the PD mice in both FST and TST, suggesting an antidepressant efficacy for the MLC901. None of the treatments alter locomotion compared to the sham group. Conclusion: In conclusion, we propose that MLC901 is a potential candidate to be used in studies for the treatment of depression in PD. 328 333 2021/01/122020/10/102020/12/312020/08/112020/11/27 1399/9/7 2021/02/82021/02/82021/02/12021/04/62021/02/8 1399/11/20 Mohaddeseh Ebrahimi-Ghiri Mohaddeseh Ebrahimi-Ghiri Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran Iran Sakineh Alijanpour Sakineh Alijanpour Department of Biology, Faculty of Science, Gonbad Kavous University, Gonbad Kavous, Iran Iran Fatemeh Khakpai Fatemeh Khakpai Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran Iran khakpai@iautmu.ac.ir Mohammad-Reza Zarrindast Mohammad-Reza Zarrindast Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran Parkinson’s disease MLC901 Forced swim test Tail suspension test Alijanpour, S., Khakpai, F., Ebrahimi-Ghiri, M., Zarrindast, M. R. (2019). 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Health and Quality of Life Outcomes, 13(1), 1–8. https://doi.org/10.1186/s12955-015-0281-x##Kamińska, K., Lenda, T., Konieczny, J., Czarnecka, A., & Lorenc-Koci, E. (2017). Depressive-like neurochemical and behavioral markers of Parkinson’s disease after 6-OHDA administered unilaterally to the rat medial forebrain bundle. Pharmacological Reports, 69(5), 985–994. https://doi.org/10.1016/j.pharep.2017.05.016##Lev, N., Barhum, Y., Ben-Zur, T., Melamed, E., Steiner, I., & Offen, D. (2013). Knocking out DJ-1 attenuates astrocytes neuroprotection against 6-hydroxydopamine toxicity. Journal of Molecular Neuroscience : MN, 50(3), 542–550. https://doi.org/10.1007/s12031-013-9984-9##Lorivel, T., Gandin, C., Veyssiere, J., Lazdunski, M., & Heurteaux, C. (2015). Positive effects of the traditional Chinese medicine MLC901 in cognitive tasks. J Neurosci Res, 93(11), 1648–1663. https://doi.org/10.1002/jnr.23591##Moha Ou Maati, H., Borsotto, M., Chatelain, F., Widmann, C., Lazdunski, M., & Heurteaux, C. (2012). Activation of ATP-sensitive potassium channels as an element of the neuroprotective effects of the Traditional Chinese Medicine MLC901 against oxygen glucose deprivation. Neuropharmacology, 63(4), 692–700. https://doi.org/10.1016/j.neuropharm.2012.05.035##Nasehi, M., Mohammadi, A., Ebrahimi-Ghiri, M., Hashemi, M., & Zarrindast, M.-R. (2019). MLC901 during sleep deprivation rescues fear memory disruption in rats. Naunyn-Schmiedeberg’s Archives of Pharmacology. https://doi.org/10.1007/s00210-018-01612-z##Negre-Pages, L., Grandjean, H., Lapeyre-Mestre, M., Montastruc, J. L., Fourrier, A., Lepine, J. P., & Rascol, O. (2010). Anxious and depressive symptoms in Parkinson’s disease: the French cross-sectionnal DoPaMiP study. 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The cardiovascular responses after lipopolysaccharide microinjection into the dorsomedial periaqueductal gray in rats 2 2 Introduction: The dorsomedial periaqueductal gray (dmPAG) is located around the cerebral aqueduct with various functions such as cardiovascular regulation and is affected by inflammation. Lipopolysaccharide (LPS) is a complex molecule with an inflammatory effect that is known to affect blood pressure. In the present study, the cardiovascular effect of LPS microinjection into the dmPAG was investigated. Methods: Rats were divided into three groups consisting of 1: control; 2: 50 ng LPS and 3:100 ng LPS. Rats were mounted on a stereotaxic device after anesthesia and a continuous recording of cardiovascular parameters was done by a PowerLab device, connected to a cannulated femoral artery and drugs microinjected into dmPAG. The changes (Δ) in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MA) and heart rate (HR) were calculated at different times and compared to the control group. Results: Both doses of LPS when microinjected into the dmPAG brought on a significant hypotensive response in the pressure parameters (MAP, SBP, and DBP) when compared to control. A non-significant increase in HR was also documented in both groups. Conclusion: The results of this experiment indicated that LPS, when microinjected into the dmPAG, induced a hypotensive response in anesthetized rats in both doses in comparison to control. 334 340 2021/01/122020/10/102020/12/312020/08/112020/11/272020/10/8 1399/7/17 2021/02/82021/02/82021/02/12021/04/62021/02/82021/02/14 1399/11/26 Reza Mohebbati Reza Mohebbati Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Iran Reza Nejad Shahrokh Abadi Reza Nejad Shahrokh Abadi Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran Vida Alikhani Vida Alikhani Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran Mohammad Naser Shafei Mohammad Naser Shafei Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Iran shafeimn@mums.ac.ir Dorsomedial periaqueductal gray Lipopolysaccharide Inflammation Blood Pressure Abadi RNS, Zangouei AS, Mohebbati R, Shafei MN. 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Peroxisome biogenesis factor 5 controlled Histone deacetylase 6 and Sirtuin1 expression and modulatedmitochondrial biogenesis in rat dorsal hippocampus 2 2 Introduction: Mitochondria and peroxisomes are tightly connected organelles that cooperate in lipid oxidation and maintenance of redox homeostasis. However, the peroxisome’s role in the modulation of the mitochondrial regulatory factors has remained unanswered. SIRT1- PGC-1α interaction as a pivotal pathway in energy expenditure leads to mitochondrial biogenesis. Histone deacetylase (HDAC)6 and HDAC10 also regulate mitochondrial dynamics. Mitochondrial dysfunction is a cause and/or consequence of aging and neurodegenerative disorders. Methods: In this study, to disturb importing proteins into the peroxisomes, PEX5 was down-regulated in the dorsal hippocampus by lentivirus-mediated shRNA. The impact of PEX5 reduction on peroxisomes was explored by assessment of catalase activity, a regular peroxisome matrix enzyme, and PMP70 and PEX14 expression. Then, mitochondrial biogenesis factors, PGC-1α, and mitochondrial transcription factor A (TFAM) were measured by quantitative polymerase chain reaction and mitochondrial-related HDACs, SIRT1, SIRT3, HDAC6 and HDAC10, by western blotting. Besides, spatial learning and memory were assessed using the Morris water maze task. Results: Our results revealed a significant reduction of HDAC6 and SIRT1, alongside with decrease in mitochondrial biogenesis factors PGC-1α and TFAM, and no alteration in HDAC10 and SIRT3. Despite all observed changes, memory performance displayed no detectable alteration in the experimental groups. These data suggest the role of peroxisomes in modulating mitochondrial dynamics via regulation of HDAC6 and SIRT1 expression. Conclusion: Peroxisome dysfunctions may occur upstream to mitochondrial failure and can be considered as a potential therapeutic target for aging and age-related disorders. 341 352 2021/01/122020/10/102020/12/312020/08/112020/11/272020/10/82021/03/16 1399/12/26 2021/02/82021/02/82021/02/12021/04/62021/02/82021/02/142021/05/1 1400/2/11 Shahrbanoo Rafiei Shahrbanoo Rafiei Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Fariba Khodagholi Fariba Khodagholi Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran khodagholi@sbmu.ac.ir Fereshteh Motamedi Fereshteh Motamedi Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Leila Dargahi Leila Dargahi Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran * Iran Peroxisome PEX5 Mitochondrial biogenesis factors Histone deacetylases Dorsal hippocampus. 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Royal jelly attenuated cognitive and non-cognitive deficits and blood-brain barrier disruption inducedby ethidium bromide 2 2 Introduction: Multiple sclerosis (MS) is an autoimmune disease. The main aims of the present investigation were to evaluate the effect of royal jelly (RJ) on cognitive and non-cognitive behavior, demyelination and the level of blood-brain barrier (BBB) disruption induced by ethidium bromide (EB). Methods: Twenty-five adult male Sprague Dawley in five groups were used. Control (intact rat); Sham (surgery without EB injection); treatment control (EB injection without treatment); treatment1 and treatment2 (orally administered of RJ 100 and 200 mg/kg/day after EB injection). EB (3μl of 0.01%) injection in the dentate gyrus (DG) was used for demyelination. Demyelination induction was proved by histological examination. For the estimation of BBB integrity, Evans blue extravasation was done using an ELISA reader. Cognitive and non-cognitive behavior was evaluated by Morris water maze. Results: Data showed that RJ corrected the deficit of demyelination. Cognitive and non-cognitive behavior improved in treatment groups relative to treatment control by RJ. The extent of BBB disruption significantly improved in treatment groups compared to the treatment control group, in the whole brain and hippocampus. Conclusion: Results indicate that RJ after EB injection in DG can improve cognitive and non-cognitive behavior, demyelination and BBB disruption in rat after EB injection. Therefore, it seems that RJ can be a supplementary drug for MS. 353 362 2021/01/122020/10/102020/12/312020/08/112020/11/272020/10/82021/03/162020/07/27 1399/5/6 2021/02/82021/02/82021/02/12021/04/62021/02/82021/02/142021/05/12021/03/15 1399/12/25 Maryam Jamali Maryam Jamali Physiology Division of Basic Science, School of Veterinary Medicine, Shiraz University, Shiraz, Iran Iran Mahnaz Taherianfard Mahnaz Taherianfard Physiology Division of Basic Science, School of Veterinary Medicine, Shiraz University, Shiraz, Iran Iran taherian@shirazu.ac.ir Mahmood Aminlari Mahmood Aminlari Biochemistry Divisions of Basic Science, School of Veterinary Medicine, Shiraz University, Shiraz, Iran Iran Jafar Jalaiee Jafar Jalaiee Pharmacology Divisions of Basic Science, School of Veterinary Medicine, Shiraz University, Shiraz, Iran Iran Royal Jelly Morris water maze Multiple sclerosis Ali AM, Kunugi H. Bee honey protects astrocytes against oxidative stress: a preliminary in vitro investigation. 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J Neurol Neurosurg Psychiatry 2012; 83: 38-43. https://doi.org/10.1136/jnnp.2010.237834##Goodman J, McIntyre CK. Impaired spatial memory and enhanced habit memory in a rat model of post-traumatic stress disorder. Front Pharmacol 2017; 8: 663. https://doi.org/10.3389/fphar.2017.00663##Goudarzvand M, Choopani S, Shams A, Javan M, Khodaii Z, Ghamsari F, et al. Focal injection of ethidium bromide as a simple model to study cognitive deficit and its improvement. Basic Clin Neurosci 2016; 7: 63-72.##Guazzo EP. A technique for producing demyelination of the rat optic nerves. J Clin Neurosci 2005; 12: 54-8. https://doi.org/10.1016/j.jocn.2004.08.002##Hattori N, Nomoto H, Fukumitsu H, Mishima S, Furukawa S. Royal jelly-induced neurite outgrowth from rat pheochromocytoma pc12 cells requires integrin signal independent of activation of extracellular signal-regulated kinases. Biomed Res 2007; 28: 139-46. https://doi.org/10.2220/biomedres.28.139##Hattori N, Ohta S, Sakamoto T, Mishima S, Furukawa S. Royal jelly facilitates restoration of the cognitive ability in trimethyltin-intoxicated mice. Evid Based Complement Alternat Med 2011; 2011: 165968. https://doi.org/10.1093/ecam/nep029##Higaki A, Mogi M, Iwanami J, Min LJ, Bai HY, Shan BS, et al. Recognition of early stage thigmotaxis in morris water maze test with convolutional neural network. PLoS One 2018; 13: e0197003. https://doi.org/10.1371/journal.pone.0197003##Illouz T, Madar R, Clague C, Griffioen KJ, Louzoun Y, Okun E. Unbiased classification of spatial strategies in the barnes maze. Bioinformatics 2016; 32: 3314-20. https://doi.org/10.1093/bioinformatics/btw376##Jonas P, Lisman J. Structure, function, and plasticity of hippocampal dentate gyrus microcircuits: Frontiers, 2015. https://doi.org/10.3389/978-2-88919-387-5##Kamakura M, Fukushima M. Inhibition of specific degradation of 57-kda protein in royal jelly during storage by ethylenediaminetetraacetic acid. Biosci Biotechnol Biochem 2002; 66: 175-78. https://doi.org/10.1271/bbb.66.175##Knezovic V, Kasprian G, Stajduhar A, Schwartz E, Weber M, Gruber GM, et al. Underdevelopment of the human hippocampus in callosal agenesis: an in vivo fetal mri study. AJNR Am J Neuroradiol 2019; 40: 576-81. https://doi.org/10.3174/ajnr.A5986##Kohno K, Okamoto I, Sano O, Arai N, Iwaki K, Ikeda M, et al. Royal jelly inhibits the production of proinflammatory cytokines by activated macrophages. Biosci Biotechnol Biochem 2004; 68: 138-45. https://doi.org/10.1271/bbb.68.138##Mahad D, Ziabreva I, Lassmann H, Turnbull D. Mitochondrial defects in acute multiple sclerosis lesions. Brain 2008; 131: 1722-35. https://doi.org/10.1093/brain/awn105##Mojaverrostami S, Bojnordi MN, Ghasemi-Kasman M, Ebrahimzadeh MA, Ghasemi Hamidabadi H. A review of herbal therapy in multiple sclerosis. 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Evaluation of the effect of silver nanoparticles onOLN-93 oligodendroglial cells 2 2 Introduction: Metals such as silver have special merit in medicine. Recently, it has been shown that silver nanoparticles (Ag-NPs) can present some properties that could be valuable for researchers because of their dual neuroprotective and neurotoxic behaviors. The present study was planned to evaluate the effect of silver nanoparticles on OLN-93 oligodendrocytes through chemical hypoxic situation. Methods: AOLN-93 cell line was selected as an oligodendroglial cell model. The stock of the tested solution contained Ag-NPs with an average size of 40nm and concentration of 20.4 ppm. Chemical hypoxic-ischemic condition was induced by sodium azide (NaN3). After a three-hour pretreatment of OLN-93 cells with Ag-NPs (0.001ppm), the cells were incubated in glucose-free medium with sodium azide (100mM and 1M) and Ag-NPs (0.001ppm) for 15min. Then, the reperfusion condition was set by returning the medium to DMEM with 10% FBS along with Ag-NPs (0.001ppm) for 24h. Next, the viability of the cells was assessed by MTT method. Also, Transmission electron microscopy images were used to evaluate the morphology of the cells. Results: Our results showed that Ag-NPs with a concentration of 0.001 ppm could significantly increase ONL-93 cells survival through the 15min hypoxic-ischemia condition induced by NaN3 (100mM) followed by reperfusion (93.02±2.83). However, Ag-NPs (0.001ppm) could not protect the cells from hypoxic-ischemic injury induced by NaN3 (1M) through the same procedure. Conclusion: Although the neurotoxic effects of Ag-NPs have been documented in many studies, the Ag-NPs solution, which was used in this study, could show protective effects on oligodendroglial cells in concentration of 0.001 ppm during the planned model of chemical ischemia. Hence, more investigation is suggested to clarify the protective effect of Ag-NPs (average size of 40 nm) on oligodendrocytes. 363 372 2021/01/122020/10/102020/12/312020/08/112020/11/272020/10/82021/03/162020/07/272020/09/29 1399/7/8 2021/02/82021/02/82021/02/12021/04/62021/02/82021/02/142021/05/12021/03/152021/02/23 1399/12/5 Shabnam Nadjafi Shabnam Nadjafi Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Iran shabnam.n@iums.ac.ir Roshanak Ghods Roshanak Ghods Research institution for Islamic and Complementary Medicine, Iran University of Medical Sciences, Tehran, Iran Iran Mehri Noori Mehri Noori Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Iran Vahid Pirhajati Mahabadi Vahid Pirhajati Mahabadi Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Iran Nasrin Hosseini Nasrin Hosseini Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Iran hosseini.n@iums.ac.ir Oligodendrocytes Silver nanoparticles TEM Ahamed M, AlSalhi M S, Siddiqui M. 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Comparison the cytotoxic effects of Ulva fasciata and Ulva lactuca on the MCF-7 and MDA-MB-231breast cancer cell lines 2 2 Introduction: Marine seaweeds has received increased attention in the protection or treatment of cancer, because of their bioactive compounds. The aim of the present study was to evaluate the anti-cancer capacity of two green seaweeds, Ulva fasciata and Ulva lactuca. Methods: The phenolic and flavonoid content of the hydro-methanolic extracts was measured, respectively by Folin-Ciocateu and aluminum chloride methods. The antioxidant activity of the extracts was evaluated by FRAP and DPPH assay and were compared to ascorbic acid. Cytotoxic effect of the extracts on the MCF-7 (ER+) and MDA-MB-231 (ER-) breast cancer cell lines was also evaluated by MTT assay after 48 and 72 hours of incubation. Results: The phenolic and flavonoid content of Ulva fasciata was respectively 14.92±1.38 μgGAE/mg and 72.15±15.4 μgQE/mg which was significantly higher than Ulva lactuca. The reducing power and radical scavenging activity of Ulva fasciata was also higher. The cytotoxic effects of Ulva fasciata on the MCF-7 and MDA-MB-231 cell lines was more than Ulva lactuca, in concentration and time dependent manner. The cytotoxic effects of the both seaweeds were more potent on the MDA-MB-231 compared to the MCF-7 cell line and indicated an estrogen and progesterone receptor independent manner of cellular growth inhibition. Conclusion: It is appeared that the Ulva fasciata extract was a better drug candidate in treatment of triple negative breast cancer due to higher antioxidant activity, phenolic and flavonoid content. Further studies in fractionation and bioactive extraction of Ulva fasciata are recommended. 373 383 2021/01/122020/10/102020/12/312020/08/112020/11/272020/10/82021/03/162020/07/272020/09/292020/08/10 1399/5/20 2021/02/82021/02/82021/02/12021/04/62021/02/82021/02/142021/05/12021/03/152021/02/232021/02/8 1399/11/20 Alireza Moulazadeh Alireza Moulazadeh Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran Razieh Ranjbar Razieh Ranjbar Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran Maryam Hekmat Maryam Hekmat Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran Iran Fatemeh Sedaghat Fatemeh Sedaghat Department of Marine Biology, Faculty of Marine Science and Technology, Hormozgan University, Bandar Abbas, Iran Iran Morteza Yousefzadi Morteza Yousefzadi Department of Biology, Faculty of Science, University of Qom, Qom, Iran Iran Sohrab Najafipour Sohrab Najafipour Medicinal Plant Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran najafipour.s@fums.ac.ir Ulva fasciata Ulva lactuca Breast cancer MTT assay Antioxidant. 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