Effectiveness of Erythropoietin on Working Memory, Passive Avoidance Learning and Anxiety- Like Behaviors in Prenatal Food Restriction Model
محورهای موضوعی : Report of Health CareNeda Bagha 1 , Mohammad Amin Edalatmanesh 2
1 - Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
2 - Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
کلید واژه: anxiety, Memory, Rat, Erythropoietin, Fetal Growth Restriction,
چکیده مقاله :
Introduction: Prenatal Food Restriction (PFR) causes some disorders in prenatal development and neuro-developmental abnormalities. On the other hand, the studies indicated that erythropoietin can act as a neuro-protector. Therefore, the aim of this study is to analyze the effects of erythropoietin on working memory, passive avoidance learning, and anxiety level in rat PFR model. Methods: In this experimental study, 50 neonatal rats are exposed to PFR. Reduction of standard food portion up to 50% has been started on the embryonic day (ED) 14 in rats until postnatal period. Then, different doses of 500, 1000, and 2000 IU/kg weight erythropoietin were injected to experimental groups, subcutaneously. At post natal day (PND) 30; Y-maze, shuttle box and elevated plus maze (EPM) are used for evaluation of working memory, passive avoidance learning, and anxiety level, respectively. Differences between groups were analyzed by one way ANOVA with Tukey’s post hoc (p ˂ 0.05). Results: The results indicate that working memory and avoidance learning have reduced significantly in the control group (p ˂ 0.05). Moreover, anxiety level has increased in PFR group in comparison with the control group (p ˂ 0.001). On the other hand, working and avoidance memories have increased in those groups which received EPO in comparison with PFR groups and anxiety level have decreased significantly (p ˂ 0.05). Conclusion: Our results indicate that prenatal treatment of erythropoietin can ameliorate behavioral abnormalities in PFR model.
1. Devaskar SU, Chu A. Intrauterine growth restriction: hungry for an answer. Physiol J. 2016; 31 (2): 131- 146.
2. Cohen E, Wong FY, Horne RS, Yiallourou SR. Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy. Pediatr Res. 2016; 79 (6): 821- 830.
3. Sharma D, Sharma P, Shastri S. Genetic, metabolic and endocrine aspect of intrauterine growth restriction: an update. J Matern Fetal Neonatal Med. 2016; 9: 1- 45.
4. Zohdi V, Lim K, Pearson JT, Black MJ. Developmental programming of cardiovascular disease following intrauterine growth restriction: findings utilising a rat model of maternal protein restriction. Nutrients. 2014; 7 (1): 119- 152.
5. Rab A, Szentpeteri I, Kornya L, Borzsonyi B, Demendi C, Gabor Joo J. Placental gene expression patterns of epidermal growth factor in intrauterine growth restriction. Eur J Obstet Gynecol Reprod Biol. 2013; 170 (1): 96- 99.
6. Akitake Y, Katsuragi S, Hosokawa M, Mishima K, Ikeda T, Miyazato M, et al. Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring. Nutr Res. 2015; 35 (1): 76- 87.
7. Chu A, Thamotharan S, Ganguly A, Wadehra M, Pellegrini M, Devaskar SU. Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction. Nutr Res. 2016; 36 (10): 1055- 1067.
8. Doyle LW. Long- term neurologic outcome for the very preterm growth- restricted fetus. Pediatrics. 2011; 127: 1048- 1049.
9. Pichon A, Jeton F, El Hasnaoui-Saadani R, Hagström L, Launay T, Beaudry M, et al. Erythropoietin and the use of a transgenic model of erythropoietin-deficient mice. Hypoxia (Auckl). 2016; 7; 4: 29- 39.
10. Almaguer- Melian W, Mercerón- Martínez D, Delgado- Ocaña S, Pavón- Fuentes N, Ledón N, Bergado JA. EPO induces changes in synaptic transmission and plasticity in the dentate gyrus of rats. Synapse. 2016; 70 (6): 240- 252.
11. Li XB, Zheng W, Ning YP, Cai DB, Yang XH, Ungvari GS, et al. Erythropoietin for Cognitive Deficits Associated with Schizophrenia, Bipolar Disorder, and Major Depression: A Systematic Review. Pharmacopsychiatry. 2018; 51(3):100-4.
12. Aalling N, Hageman I, Miskowiak K, Orlowski D, Wegener G, Wortwein G. Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminals-relation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats. J Neurosci Res. 2017; 96 (1): 103- 116.
13. Wang H , Fan J, Chen M, Yao Q, Gao Z, Zhang G, et al. rhEPO enhances cellular anti- oxidant capacity to protect long- term cultured aging primary nerve cells. J Mol Neurosci. 2017; 62 (3- 4): 291- 303.
14. Peng W, Xing Z, Yang J, Wang Y, Wang W, Huang W. The efficacy of erythropoietin in treating experimental traumatic brain injury: a systematic review of controlled trials in animal models. J Neurosurg. 2014; 121 (3): 653- 664.
15. He Z, Lv F, Ding Y, Zhu C, Huang H, Zhang L, et al. Insulin- like growth factor 1 mediates adrenal development dysfunction in offspring rats induced by prenatal food restriction. Arch Med Res. 2017; 48 (6): 488- 497.
16. Hongying H, Xiauyu Q, Suisheng W. Carbamylated erythropoietin attenuates cardiomyopathy via PI3K/Akt activation in rats with diabetic cardiomyopathy. Exp Ther Med. 2013; 6 (2): 567– 573.
17. Edalatmanesh M A, Yazdani M, Davoodi A, Rafiei S. Anxiolytic Effect of Lithium Chloride in Model of PTZ-Induced Seizure. Horizon Med Sci . 2018; 24 (2):79-87.
18. Edalatmanesh M A, sahraeian S, Rafiei S. The effect of sodium butyrate, histone deacetylase inhibitor on spatial learning and memory in rat model of cerebral hypoxic-ischemia. Med Sci. 2018; 28 (1):16-23.
19. Edalatmanesh MA, Nikfarjam H, Moghadas M, Haddad- Mashadrizeh A, Robati R, et al. 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- 334.
20. Wixey JA, Chand KK, Colditz PB, Bjorkman ST. Review: neuroinflammation in intrauterine growth restriction. Placenta. 2017; 54: 117- 124.
21. Bruno CJ, Bengani S, Gomes WA, Brewer M, Vega M, Xie X, et al. MRI differences associated with intrauterine growth restriction in preterm infants. Neonatology. 2017; 111 (4): 317- 323.
22. Boubred F, Delamaire E, Buffat C, Daniel L, Boquien CY, Darmaun D, et al. High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR. Pediatr Res. 2016; 79 (1): 22- 26
23. Duran Fernandez- Feijoo C, Carrasco Carrasco C, Villalmazo Francisco N, Cebrià Romero J, Fernández Lorenzo JR, Jiménez-Chillaron JC, et al. Influence of catch up growth on spatial learning and memory in a mouse model of intrauterine growth restriction. PLoS One. 2017; 24; 12 (5): e0177468.
24. Illa M, Eixarch E, Batalle D, Arbat- Plana A, Muñoz- Moreno E, et al. Long-term functional outcomes and correlation with regional brain connectivity by MRI diffusion tractography metrics in a near-term rabbit model of intrauterine growth restriction. PLoS One. 2013; 8 (10): e76453.
25. Zinkhan EK, Yu B, Callaway CW, McKnight RA. Intrauterine growth restriction combined with a maternal high-fat diet increased adiposity and serum corticosterone levels in adult rat offspring. J Dev Orig Health Dis. 2018; 9(3):315-28.
26. Naik AA, Patro IK, Patro N. Slow physical growth, delayed reflex ontogeny, and permanent behavioral as well as cognitive impairments in rats following intra- generational protein malnutrition. Front Neurosci. 2015; 9: 446.
27. Nekoui A, Blaise G. Erythropoietin and nonhematopoietic effects. Am J Med Sci. 2017; 353 (1): 76- 81.
28. Zhou ZW, Li F, Zheng ZT, Li YD, Chen TH, Gao WW, et al. Erythropoietin regulates immune/inflammatory reaction and improves neurological function outcomes in traumatic brain injury. Brain Behav. 2017; 37 (11): e0082722.
29. Ercan I, Tufekci KU, Karaca E, Genc S, Genc K. Peptide Derivatives of Erythropoietin in the Treatment of Neuroinflammation and Neurodegeneration. Adv Protein Chem Struct Biol. 2018; 112:309-57.
30. Eixarch E, Muñoz- Moreno E, Bargallo N, Batalle D, Gratacos E. Motor and cortico- striatal-thalamic connectivity alterations in intrauterine growth restriction. Am J Obstet Gynecol. 2016; 214 (6): 725.e1-9.
31. Hattori Y, Takeda T, Fujii M, Taura J, Ishii Y, Yamada H. Dioxin-induced fetal growth retardation: the role of a preceding attenuation in the circulating level of glucocorticoid. Endocrine. 2014; 47 (2): 572- 580.
32. Numakawa T, Matsumoto T, Ooshima Y, Chiba S, Furuta M, Izumi A, et al. Impairments in brain-derived neurotrophic factor-induced glutamate release in cultured cortical neurons derived from rats with intrauterine growth retardation: possible involvement of suppression of TrkB/phospholipase C-γ activation. Neurochem Res. 2014; 39 (4): 785- 792.
33. Malamitsi- Puchner A, Nikolaou KE, Puchner KP. Intrauterine growth restriction, brain-sparing effect, and neurotrophins. Ann N Y Acad Sci. 2006; 1092: 293- 296.