Abstract
Rationale
Post-traumatic stress disorder (PTSD) is a psychiatric disorder developed after an exposure to severe traumatic events. Patients with PTSD suffer from different symptoms including memory impairment. In addition, PTSD is associated with oxidative stress. Vitamin E, a fat-soluble vitamin, possesses cognition protective effects via its antioxidative properties.
Objectives
To investigate the impact of vitamin E on memory impairment induced by PTSD in animals.
Methods
A rat model of PTSD-like behavior and the radial arm water maze (RAWM) for testing of learning and memory paradigm were used. Rats were divided into 4 groups: control, vitamin E, PTSD, and vitamin E + PTSD.
Results
In the learning phase, results showed no significant differences among experimental groups, indicating that PTSD-like behavior did not impair learning ability in rats. However, memory tests in the RAWM showed that PTSD-like animals had impairment in both short-term and long-term memories. Vitamin E, on the other hand, prevented this impairment of memory. With respect to oxidative stress, significant decreases were detected in reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, glutathione peroxidase (GPx) and catalase enzyme activities, global histone 3 acetylation, and brain derived neurotrophic factor (BDNF) levels in the PTSD-like animals group compared with other groups (P < 0.05). Vitamin E protected the reduction of these oxidative stress biomarkers, global histone 3 acetylation, and BDNF levels.
Conclusions
Vitamin E prevented memory impairment associated with PTSD-like behavior in animals, probably via its antioxidative properties, and preservation of epigenetic changes induced in PTSD-like animals.
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References
Alqudah MAY, Al-Ashwal FY, Alzoubi KH, Alkhatatbeh M, Khabour O (2018) Vitamin E protects human lymphocytes from genotoxicity induced by oxaliplatin. Drug Chem Toxicol 41:281–286. https://doi.org/10.1080/01480545.2017.1384835
Alzoubi KH, Al-Ibbini AM, Nuseir KQ (2018a) Prevention of memory impairment induced by post-traumatic stress disorder by cerebrolysin. Psychiatry Res 270:430–437. https://doi.org/10.1016/j.psychres.2018.10.008
Alzoubi KH, Al Subeh ZY, Khabour OF (2017) Evaluating the protective effect of etazolate on memory impairment, anxiety- and depression-like behaviors induced by post traumatic stress disorder. Brain Res Bull 135:185–192. https://doi.org/10.1016/j.brainresbull.2017.10.012
Alzoubi KH et al. (2019) Vitamin E modifies high-fat diet-induced reduction of seizure threshold in rats: role of oxidative stress Physiol Behav 206:200-205
Alzoubi KH, Khabour OF, Ahmed M (2018b) Pentoxifylline prevents post-traumatic stress disorder induced memory impairment. Brain Res Bull 139:263–268. https://doi.org/10.1016/j.brainresbull.2018.03.009
Alzoubi KH, Khabour OF, Rashid BA, Damaj IM, Salah HA (2012a) The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: the role of oxidative stress. Behav Brain Res 226:205–210. https://doi.org/10.1016/j.bbr.2011.09.017
Alzoubi KH, Khabour OF, Rashid BA, Damaj IM, Salah HA (2012b) The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: the role of oxidative stress. Behav Brain Res 226:205–210
Alzoubi KH, Khabour OF, Salah HA, Hasan Z (2013a) Vitamin E prevents high-fat high-carbohydrates diet-induced memory impairment: the role of oxidative stress. Physiol Behav 119:72–78. https://doi.org/10.1016/j.physbeh.2013.06.011
Alzoubi KH, Khabour OF, Salah HA, Hasan Z (2013b) Vitamin E prevents high-fat high-carbohydrates diet-induced memory impairment: the role of oxidative stress. Physiol Behav 119:72–78
Alzoubi KH, Khabour OF, Tashtoush NH, Al-Azzam SI, Mhaidat NM (2013c) Evaluation of the effect of pentoxifylline on sleep-deprivation induced memory impairment. Hippocampus 23:812–819. https://doi.org/10.1002/hipo.22135
Alzoubi KH, Rababa'h AM, Al Yacoub ON (2018c) Tempol prevents post-traumatic stress disorder induced memory impairment. Physiol Behav 184:189–195. https://doi.org/10.1016/j.physbeh.2017.12.002
Andero R, Daviu N, Escorihuela RM, Nadal R, Armario A (2012) 7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats. Hippocampus 22:399–408. https://doi.org/10.1002/hipo.20906
Asha Devi S, Manjula K, Subramanyam M (2012) Protective role of vitamins E and C against oxidative stress caused by intermittent cold exposure in aging rat’s frontoparietal cortex. Neurosci Lett 529:155–160
Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64:238–258. https://doi.org/10.1124/pr.111.005108
Borghans B, Homberg JR (2015) Animal models for posttraumatic stress disorder: an overview of what is used in research. World J Psychiatry 5:387–396. https://doi.org/10.5498/wjp.v5.i4.387
Bousiges O et al (2013) Detection of histone acetylation levels in the dorsal hippocampus reveals early tagging on specific residues of H2B and H4 histones in response to learning. PLoS One 8:e57816. https://doi.org/10.1371/journal.pone.0057816
Busari AA, Adejare AA, Shodipe AF, Oduniyi OA, Ismail-Badmus KB, Oreagba IA (2018) Protective but non-synergistic effects of Nigella Sativa and vitamin E against cisplatin-induced renal toxicity and oxidative stress in Wistar rats. Drug Res 68:696–703
Chen CV, Chaby LE, Nazeer S, Liberzon I (2018) Effects of trauma in adulthood and adolescence on fear extinction and extinction retention: advancing animal models of posttraumatic stress disorder. Front Behav Neurosci 12:247. https://doi.org/10.3389/fnbeh.2018.00247
Cohen H, Kaplan Z, Matar MA, Loewenthal U, Zohar J, Richter-Levin G (2007) Long-lasting behavioral effects of juvenile trauma in an animal model of PTSD associated with a failure of the autonomic nervous system to recover. Eur Neuropsychopharmacol 17:464–477. https://doi.org/10.1016/j.euroneuro.2006.11.003
Comin D, Gazarini L, Zanoni JN, Milani H, de Oliveira RMW (2010) Vitamin E improves learning performance and changes the expression of nitric oxide-producing neurons in the brains of diabetic rats. Behav Brain Res 210:38–45. https://doi.org/10.1016/j.bbr.2010.02.001
Dagnas M, Micheau J, Decorte L, Beracochea D, Mons N (2014) Post-training, intrahippocampal HDAC inhibition differentially impacts neural circuits underlying spatial memory in adult and aged mice. Hippocampus. https://doi.org/10.1002/hipo.22406
Dunlop BW, Wong A (2019) The hypothalamic-pituitary-adrenal axis in PTSD: pathophysiology and treatment interventions. Prog Neuro-Psychopharmacol Biol Psychiatry 89:361–379
El-Elimat T, Alzoubi KH, AbuAlSamen MM, Al Subeh ZY, Graf TN, Oberlies NH (2019) Silymarin prevents memory impairments, anxiety, and depressive-like symptoms in a rat model of post-traumatic stress disorder. Planta Med 85:32–40. https://doi.org/10.1055/a-0710-5673
Farbstein D et al (2011) Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype. Atherosclerosis 219:240–244
Ford JM, Brandt NJ (2014) Role of nutraceuticals in dementia care. J Gerontol Nurs 40:11–17
Fuchikami M, Morinobu S, Kurata A, Yamamoto S, Yamawaki S (2009) Single immobilization stress differentially alters the expression profile of transcripts of the brain-derived neurotrophic factor (BDNF) gene and histone acetylation at its promoters in the rat hippocampus. Int J Neuropsychopharmacol 12:73–82. https://doi.org/10.1017/s1461145708008997
Garza AA, Ha TG, Garcia C, Chen MJ, Russo-Neustadt AA (2004) Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain. Pharmacol Biochem Behav 77:209–220
Gugliandolo A, Bramanti P, Mazzon E (2017) Role of vitamin E in the treatment of Alzheimer’s disease: evidence from animal models. Int J Mol Sci:18. https://doi.org/10.3390/ijms18122504
Gurel A, Coskun O, Armutcu F, Kanter M, Ozen OA (2005) Vitamin E against oxidative damage caused by formaldehyde in frontal cortex and hippocampus: biochemical and histological studies. J Chem Neuroanat 29:173–178. https://doi.org/10.1016/j.jchemneu.2005.01.001
Hei Y, Chen R, Yi X, Wei L, Long Q, Liu W (2018) The expression of hippocampal NRG1/ErbB4 correlates with neuronal apoptosis, but not with glial activation during chronic cerebral hypoperfusion. Front Aging Neurosci 10:149. https://doi.org/10.3389/fnagi.2018.00149
Hutchinson KM et al (2012) Environmental enrichment protects against the effects of chronic stress on cognitive and morphological measures of hippocampal integrity. Neurobiol Learn Mem 97:250–260. https://doi.org/10.1016/j.nlm.2012.01.003
Khan S, Liberzon I (2004) Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD Psychopharmacology (Berl) 172:225-229 https://doi.org/10.1007/s00213-003-1634-4
Knox D, George SA, Fitzpatrick CJ, Rabinak CA, Maren S, Liberzon I (2012) Single prolonged stress disrupts retention of extinguished fear in rats. Learn Mem 19:43–49. https://doi.org/10.1101/lm.024356.111
La Fata G, Weber P, Mohajeri MH (2014) Effects of vitamin E on cognitive performance during ageing and in Alzheimer’s disease. Nutrients 6:5453–5472. https://doi.org/10.3390/nu6125453
Li G et al (2017) Beneficial effect of fluoxetine treatment aganist psychological stress is mediated by increasing BDNF expression in selected brain areas. Oncotarget 8:69527–69537. https://doi.org/10.18632/oncotarget.17891
Liberzon I, Lopez JF, Flagel SB, Vazquez DM, Young EA (1999) Differential regulation of hippocampal glucocorticoid receptors mRNA and fast feedback: relevance to post-traumatic stress disorder. J Neuroendocrinol 11:11–17. https://doi.org/10.1046/j.1365-2826.1999.00288.x
Lin CC et al (2019) Subchronic administration of aripiprazole improves fear extinction retrieval of Pavlovian conditioning paradigm in rats experiencing psychological trauma. Behav Brain Res 362:181–187. https://doi.org/10.1016/j.bbr.2018.12.051
Lipsky RH (2013) Epigenetic mechanisms regulating learning and long-term memory International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 31:353-358 https://doi.org/10.1016/j.ijdevneu.2012.10.110
Liu H, Atrooz F, Salvi A, Salim S (2017) Behavioral and cognitive impact of early life stress: insights from an animal model. Prog Neuro-Psychopharmacol Biol Psychiatry 78:88–95. https://doi.org/10.1016/j.pnpbp.2017.05.015
Mhaidat NM, Alzoubi KH, Khabour OF, Tashtoush NH, Banihani SA, Abdul-razzak KK (2015) Exploring the effect of vitamin C on sleep deprivation induced memory impairment. Brain Res Bull 113:41–47. https://doi.org/10.1016/j.brainresbull.2015.02.002
Mitchell JB, Samuni A, Krishna MC, DeGraff WG, Ahn MS, Samuni U, Russo A (1990) Biologically active metal-independent superoxide dismutase mimics. Biochemistry 29:2802–2807
Nuseir KQ, Alzoubi KH, Alhusban A, Bawaane A, Al-Azzani M, Khabour OF (2017) Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: role of BDNF and beta-endorphin. Physiol Behav 179:213–219. https://doi.org/10.1016/j.physbeh.2017.06.015
Peretto P, Paredes RG (2014) Frontiers in Neuroscience Social cues, adult neurogenesis, and reproductive behavior. In: Mucignat-Caretta C (ed) Neurobiology of Chemical Communication. CRC Press (c) 2014 by Taylor & Francis Group, LLC., Boca Raton (FL),
Solanki N, Alkadhi I, Atrooz F, Patki G, Salim S (2015) Grape powder prevents cognitive, behavioral, and biochemical impairments in a rat model of posttraumatic stress disorder. Nutr Res 35:65–75
Tuzcu M, Baydas G (2006) Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats. Eur J Pharmacol 537:106–110. https://doi.org/10.1016/j.ejphar.2006.03.024
Ulatowski LM, Manor D (2015) Vitamin E and neurodegeneration. Neurobiol Dis 84:78–83. https://doi.org/10.1016/j.nbd.2015.04.002
Vanelzakker MB, Zoladz PR, Thompson VM, Park CR, Halonen JD, Spencer RL, Diamond DM (2011) Influence of pre-training predator stress on the expression of c-fos mRNA in the hippocampus, amygdala, and striatum following long-term spatial memory retrieval. Front Behav Neurosci 5:30. https://doi.org/10.3389/fnbeh.2011.00030
Wang SC, Lin CC, Chen CC, Tzeng NS, Liu YP (2018) Effects of oxytocin on fear memory and neuroinflammation in a rodent model of posttraumatic stress disorder. Int J Mol Sci:19. https://doi.org/10.3390/ijms19123848
Wilson CB, McLaughlin LD, Nair A, Ebenezer PJ, Dange R, Francis J (2013) Inflammation and oxidative stress are elevated in the brain, blood, and adrenal glands during the progression of post-traumatic stress disorder in a predator exposure animal model. PLoS One 8:e76146. https://doi.org/10.1371/journal.pone.0076146
Woldemichael BT, Bohacek J, Gapp K, Mansuy IM (2014) Epigenetics of memory and plasticity progress in molecular biology and translational science 122:305-340 doi:https://doi.org/10.1016/B978-0-12-420170-5.00011-8
Wolf G et al (2017) Differentially severe cognitive effects of compromised cerebral blood flow in aged mice: association with myelin degradation and microglia activation. Front Aging Neurosci 9:191. https://doi.org/10.3389/fnagi.2017.00191
Yang F, Wolk A, Hakansson N, Pedersen NL, Wirdefeldt K (2017) Dietary antioxidants and risk of Parkinson’s disease in two population-based cohorts. Mov Disord 32:1631–1636
Yatin SM, Varadarajan S, Butterfield DA (2000) Vitamin E prevents Alzheimer’s amyloid ß-peptide (1-42)-induced neuronal protein oxidation and reactive oxygen species production. J Alzheimers Dis 2:123–131
Funding
Financial Support was via grant number 232/2014 from the Deanship of Research at the Jordan University of Science and Technology to KA. MA received a scholarship from DAAD (German Academic Exchange Service) to pursue his masters at the Jordan University of Science and Technology.
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The study protocol was approved by the Institutional Animal Care and Use Committee of the Jordan University of Science and Technology (Protocol approval number 16/3/3/460).
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Ahmed, M., Alzoubi, K.H. & Khabour, O.F. Vitamin E prevents the cognitive impairments in post-traumatic stress disorder rat model: behavioral and molecular study. Psychopharmacology 237, 599–607 (2020). https://doi.org/10.1007/s00213-019-05395-w
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DOI: https://doi.org/10.1007/s00213-019-05395-w