The Effect of Erythropoietin on Spatial Memory and Entorhinal Cerebrocortical Level of BDNF in Rat Model of Intrauterine Growth Restriction

Document Type : Original Article

Authors

Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran

Abstract

Introduction: Intrauterine Growth Restriction (IUGR) causes disruption for the central nervous system of fetus and is followed by cerebral cortex damage of neonates. This study aims to analyze the effects of erythropoietin (EPO) on spatial memory and brain-derived neurotrophic factor (BDNF) in entorhinal cortex of IUGR rat models. Methods: For IUGR induction, anterior uterine artery occlusion surgery is carried out on rats in embryonic day (ED) 14. From ED12, EPO are injected subcutaneously in 500, 1000 and 2000 IU/kg doses until the birth of their neonates. Spatial memory is analyzed by Morris water maze at postnatal day (PND) 30. Then, BDNF cerebral cortex level is estimated using ELISA. Differences between groups is analyzed with ANOVA and considered statistically significant at p ≤ 0.05. Results: A significant decrease is observed in spatial memory and BDNF cortex of untreated IUGR group in comparison with the control group (p ≤ 0.05). On the other hand, treatment of EPO improves spatial memory by increasing BDNF level in entorhinal cortex (p ≤0.05). Conclusion: The present study indicates that fetal growth restriction causes cognitive disorder in rat model. Consequently, expression of neurotrophic factors, such as cerebral cortical BDNF, will be decreased. Moreover, neuroprotective effects of EPO could ameliorate cognitive deficits in IUGR model.

Keywords

References

  1. 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.
  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. Vaiserman AM. Birth weight predicts aging trajectory: A hypothesis. Mech Ageing Dev. 2018; 173: 61- 70.
  4. Carducci B, Bhutta ZA. Care of the growth-restricted newborn. Best Pract Res Clin Obstet Gynaecol. 2018; 49: 103- 116.
  5. Tauber M. Final height and intrauterine growth retardation. Ann Endocrinol (Paris). 2017; 78 (2): 96- 97.
  6. Devaskar SU, Chu A.. Intrauterine growth restriction: hungry for an answer. Physiology (Bethesda). 2016; 31 (2): 131- 146.
  7. Morgan TK. Role of the placenta in preterm birth: a review. Am J Perinatol. 2016; 33 (3): 258- 266.
  8. Sankaran S, Kyle PM. Aetiology and pathogenesis of IUGR. Best Pract Res Clin Obstet Gynaecol. 2009; 23 (6): 765- 777.
  9. Limesand SW, Rozance PJ. Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency. J Physiol. 2017; 595 (15): 5103- 5113.
  10. Vázquez-Gómez M, Valent D, García-Contreras C, Arroyo L, Óvilo C, Isabel B, Bassols A, González-Bulnes A. Sex and intrauterine growth restriction modify brain neurotransmitters profile of newborn piglets. Int J Dev Neurosci. 2016; 9 (55): 9- 14.
  11. Chen J, Chen P, Bo T, Luo K. Cognitive and behavioral outcomes of intrauterine growth restriction school- age children. Pediatrics. 2016; 137 (4): e20153868.
  12. Epstein RA, Patai EZ, Julian JB, Spiers HJ. The cognitive map in humans: spatial navigation and beyond. Nat Neurosci. 2017; 20 (11): 1504- 1513.
  13. Witter MP, Doan TP, Jacobsen B, Nilssen ES, Ohara S. Architecture of the entorhinal cortex a review of entorhinal anatomy in rodents with some comparative notes. Front Syst Neurosci. 2017; 11: 46.
  14. Igarashi KM. The entorhinal map of space. Brain Res. 2016; 1637: 177- 187.
  15. Malamitsi-Puchner A, Nikolaou KE, Puchner KP. Intrauterine growth restriction, brain-sparing effect, and neurotrophins. Ann N Y Acad Sci. 2006; 1092: 293- 296.
  16. Campeau S, Liberzon I, Morilak D, Ressler K. Stress modulation of cognitive and affective processes. Stress. 2011; 14 (5): 503- 519.
  17. Selles MC, Oliveira MM, Ferreira ST. Brain inflammation connects cognitive and non- cognitive symptoms in alzheimer's disease. J Alzheimers Dis. 2018; 64 (s1): S313- S327.
  18. Djordjevic J, Thomson E, Chowdhury SR, Snow WM, Perez C, Wong TP, et al. Brain region- and sex-specific alterations in mitochondrial function and NF-κB signaling in the TgCRND8 mouse model of Alzheimer's disease. Neuroscience. 2017; 361: 81- 92.
  19. 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.
  20. 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.
  21. Dikmen A, Ergenoglu AM, Yeniel AO, Dilsiz OY, Ercan G, Yilmaz H. Evaluation of glycemic and oxidative/antioxidative status in the estradiol valerate-induced PCOS model of rats. Eur J Obstet Gynecol Reprod Biol. 2012; 160 (1): 55- 59.
  22. Janot M, Cortes-Dubly ML, Rodriguez S, Huynh-Do U. Bilateral uterine vessel ligation as a model of intrauterine growth restriction in mice. Reprod Biol Endocrinol. 2014; 12 (1): 62.
  23. 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.
  24. Edalatmanesh MA, 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.
  25. Simões RV, Muñoz-Moreno E, Cruz-Lemini M, Eixarch E, Bargalló N, Sanz-Cortés M, et al. Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome. Am J Obstet Gynecol. 2017; 216 (1): 62.e1- 62.e14.
  26. Wixey JA, Chand KK, Colditz PB, Bjorkman ST. Review: neuroinflammation in intrauterine growth restriction. Placenta. 2017; 54: 117- 124.
  27. Akitake Y, Katsuragi S, Hosokawa M, Mishima K, Ikeda T, Miyazato M, Hosoda H. Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring. Nutr Res. 2015; 35 (1): 76- 87.
  28. Doyle LW. Long-term neurologic outcome for the very preterm growth-restricted fetus. Pediatrics. 2011; 127: 1048- 1049.
  29. Miller AM, Vedder LC, Law LM, Smith DM. Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition. Front Hum Neurosci. 2014; 8: 586.
  30. Braun DJ, Kalinin S, Feinstein DL. Conditional depletion of hippocampal brain- derived neurotrophic factor eacerbates neuropathology in a mouse model of alzheimer's disease. ASN Neuro. 2017; 9 (2): 1759091417696161.
  31. Waterhouse EG, Xu B. The skinny on brain-derived neurotrophic factor: evidence from animal models to GWAS. J Mol Med (Berl). 2013; 91 (11): 1241- 1247.
  32. Santana-Martínez RA, León-Contreras JC, Barrera-Oviedo D, Pedraza-Chaverri J, Hernández-Pando R, Maldonado PD. Sustained activation of JNK induced by quinolinic acid alters the BDNF/TrkB axis in the rat striatum. Neuroscience. 2018; 383: 22- 32.
  33. Jia Z, Xue R, Ma S, Xu J, Guo S, Li S, et al. Erythropoietin attenuates the memory deficits in aging rats by rescuing the oxidative stress and inflammation and promoting BDNF releasing. Mol Neurobiol. 2016; 53 (8): 5664- 5670.
  34. Mahmood A, Lu D, Qu C, Goussev A, Zhang ZG, Lu C, Chopp M. Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin. J Neurosurg. 2007; 107 (2): 392- 397.
Report of Health Care
Volume 4, Issue 1
March 2018
Pages 1-8

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