Volume 11, Issue 4 (Jul-Aug 2017)                   mljgoums 2017, 11(4): 39-44 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mahmoodi M, Zeini M, Shahidi S. Effect of Letrozole during Pregnancy on Learning and Memory of Offspring Rats. mljgoums 2017; 11 (4) :39-44
URL: http://mlj.goums.ac.ir/article-1-1026-en.html
1- Department of Biology, Islamic Azad University, Hamadan Branch, Hamadan, Iran , minoomahmoodi@yahoo.com
2- Department of Biology, Islamic Azad University, Hamadan Branch, Hamadan, Iran
3- Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
Abstract:   (8163 Views)
ABSTRACT
       Background and Objectives: Hippocampus is the main structure involved in spatial learning and memory consolidation. Formation of spatial memory can be strongly influenced by medications, hormones and different substances. Due to importance of new pharmacotherapy on drug administration in pregnancy, the aim of this study was to investigate the effect of letrozole-therapy during pregnancy on memory and learning in offspring rats.
       Methods: In this study, 24 pregnant rats were divided into a control and three experimental groups (N=6). The subjects received low dose (0.25 mg/Kg), average dose (0.5 mg/Kg) and high dose (1 mg/Kg) of letrozole orally during 16-19 days of gestation. After maturating, learning and memory of the offspring were assessed by passive avoidance learning apparatus. Data were analyzed by SPSS 20 using one-way analysis of variance and the Tukey's test. P-values less than 0.05 were considered statistically significant.
         Results: Weights of the offspring who received letrozole decreased significantly compared with the control. There was no significant difference in the step-through latency between the experimental groups. However, the step-through latency and time spent in the dark compartment decreased significantly in the experimental groups compared with control group (P<0.05).
          Conclusion: The results of this study show that letrozole can influence learning and memory of offspring rats.
          Keywords: Letrozole, Gestation, Memory, Learning, Offspring, Rats.
Full-Text [PDF 468 kb]   (1197 Downloads)    
Research Article: Original Paper |
Received: 2017/12/17 | Accepted: 2017/12/17 | Published: 2017/12/17 | ePublished: 2017/12/17

References
1. Tiboni GM, Marotta F, Castigliego AP, Rossi C. Impact of estrogen replacement on letrozole-induced embryopathic effects. Hum Reprod. 2009; 24(11): 2688-92. doi: 10.1093/humrep/dep277. [DOI:10.1093/humrep/dep277]
2. Mohamed I, Yeh JK. Alfacalcidol prevents aromatase inhibitor (Letrozole)-induced bone mineral loss in young growing female rats. J Endocrinol. 2009; 202(2): 317-25. doi: 10.1677/JOE-08-0532. [DOI:10.1677/JOE-08-0532]
3. Albrecht ED, Lane MV, Marshall GR, Merchenthaler I, Simorangkir DR, Pohl CR , et al. Estrogen promotes germ cell and seminiferous tubule development in the baboon fetal testis. BiolReprod.2009; 81(2): 406-14. doi: 10.1095/biolreprod.108.073494. [DOI:10.1095/biolreprod.108.073494]
4. Aydin M, Yilmaz B, Alcin E, Nedzvetsky VS, Sahin Z, Tuzcu M. Effects of letrozole on hippocampal and cortical catecholaminergic neurotransmitter levels, neural cell adhesion molecule expression and spatial learning and memory in female rats. Neuroscience. 2008; 151(1): 186-194. [DOI:10.1016/j.neuroscience.2007.09.005]
5. Garcia-Segura LM, Azcoitia I, DonCarlos LL. Neuroprotection by estradiol. Prog Neurobiol. 2001; 63(1): 29-60. [DOI:10.1016/S0301-0082(00)00025-3]
6. Lee SJ, McEwen BS. Neurotrophic and neuroprotective actions of estrogens and their therapeutic implications. Annu Rev Pharmacol Toxicol. 2001; 41: 569-591. DOI:10.1146/annurev.pharmtox.41.1.569. [DOI:10.1146/annurev.pharmtox.41.1.569]
7. Bian C, Zhao Y, Guo Q, Xiong Y, Cai W, Zhang J. Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocrine and integration. J Steroid Biochem Mol Biol. 2014; 141: 37-43. [DOI:10.1016/j.jsbmb.2013.12.020]
8. Hajszan T, MacLusky NJ, Johansen JA, Jordan CL, Leranth C. Effects of androgens and estradiol on spine synapse formation in the prefrontal cortex of normal and testicular feminization mutant male rats. Endocrinology. 2007; 148(5): 1963-1967. [DOI:10.1210/en.2006-1626]
9. Hojo Y, Hattori TA, Enami T, Furukawa A, Suzuki K, Ishii HT, Kawato S. Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons. Proc Natl Acad Sci. 2004; 101(3): 865-870. [DOI:10.1073/pnas.2630225100]
10. Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. J Comp Neurol. 1997; 388(4): 507-525. 10.
11. Kawas C, Resnick S, Morrison A, Brookmeyer R, Corrada M, Zonderman A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology. 1997; 48(6): 1517-1521. [DOI:10.1212/WNL.48.6.1517]
12. MacLusky NJ, Walters MJ, Clark AS, Toran-Allerand CD. Aromatase in the cerebral cortex, hippocampus, and mid-brain: ontogeny and developmental implications. Mol Cell Neurosci. 1994; 5(6): 691-698. [DOI:10.1006/mcne.1994.1083]
13. Roselli CE, Horton LE, Resko JA. Distribution and regulation of aromatase activity in the rat hypothalamus and limbic system. Endocrinology. 1985; 117(6): 2471-2477. [DOI:10.1210/endo-117-6-2471]
14. Brodie A, Lu Q, Long B. Aromatase and its inhibitors. J Steroid Biochem Mol Biol. 1999; 69(1-6): 205-210. [DOI:10.1016/S0960-0760(99)00051-5]
15. Jenkins V, Shilling V, Fallowfield L, Howell A, Hutton S. Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study. Psychooncology. 2004; 13(1): 61-66. [DOI:10.1002/pon.709]
16. Kucherov A, Polotsky AJ, Menke M, Isaac B, McAvey B, Buyuk E, Santoro N. Aromatase inhibition causes increased amplitude, but not frequency, of hypothalamic-pituitary output in normal women. Fertil Steril. 2011; 95(6): 2063-2066. [DOI:10.1016/j.fertnstert.2011.01.158]
17. Wickman S, Dunkel L. Inhibition of P450 aromatase enhances gonadotropin secretion in early and midpubertal boys: evidence for a pituitary site of action of endogenous E. J Clin Endocrinol Metab. 2001; 86(10): 4887-4894. [DOI:10.1210/jcem.86.10.7927]
18. Meng FT, Ni RJ, Zhang Z, Zhao J, Liu YJ, Zhou JN. Inhibition of oestrogen biosynthesis induces mild anxiety in C57BL/6J ovariectomized female mice. Neurosci Bull. 2011; 27(4): 241-250. [DOI:10.1007/s12264-011-1014-8]
19. Cost KT, Lobell TD, Williams-Yee ZN, Henderson S, Dohanich G. The effects of pregnancy, lactation, and primiparity on object-in-place memory of female rats. Horm Behav. 2014; 65(1): 32-39. [DOI:10.1016/j.yhbeh.2013.10.012]
20. Macbeth AH, Luine VN. Changes in anxiety and cognition due to reproductive experience: a review of data from rodent and human mothers. [Review]. Neurosci Biobehav Rev. 2010; 34(3): 452-467. doi: 10.1016/j.neubiorev.2009.08.011. [DOI:10.1016/j.neubiorev.2009.08.011]
21. Gong J, Wu DB, Zhang LL, Li J, Zhao X, Zhang D. Study on the oxidative stress in the ovaries of a rat model of polycystic ovary. Sichuan Da XueBao Yi Xue Ban. 2015; 46(2): 238-42.
22. Gozukara IO, Pınar N, Ozcan O, Ozgur T, Dokuyucu R, Kurt RK, et al. Effect of colchicine on polycystic ovary syndrome: an experimental study. Gynecologic Endocrinology and Reproductive Medicine, Archives of Gynecology and Obstetrics. 2015; (2): 1-6.
23. Xu XJ, Zhang HF, Shou XJ, Li J, Jing WL, Zhou Y, et al. Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring. PhysiolBehav. 2014; 138: 13-20. doi: 10.1016/j.physbeh.2014.09.014. [DOI:10.1016/j.physbeh.2014.09.014]
24. Shahidi S, Komaki A, Mahmoodi M, Lashgari R. The role of GABAergic transmission in the dentate gyrus on acquisition, consolidation and retrieval of an inhibitory avoidance learning and memory task in the rat. Brain Res. 2008; 1204: 87-93. [DOI:10.1016/j.brainres.2008.02.008]
25. Khodamoradi N, Komaki A, Salehi I, Shahidi S, Sarihi A. Effect of vitamin E on lead exposure-induced learning and memory impairment in rats. Physiol Behav. 2015; 144: 90-94. doi: 10.1016/j.physbeh.2015.03.015. [DOI:10.1016/j.physbeh.2015.03.015]
26. Kipp M, Karakaya S, Pawlak J, Araujo-Wright G, Arnold S, Beyer C. Estrogen and the development and protection of nigrostriatal dopaminergic neurons: concerted action of a multitude of signals, protective molecules, and growth factors. Front Neuroendocrinol. 2006; 27(4): 376-390. [DOI:10.1016/j.yfrne.2006.07.001]
27. Shilling V, Jenkins V, Fallowfield L, & Howell A. The effects of oestrogens and anti-oestrogens on cognition. Breast. 2001; 10(6): 484-491. DOI:10.1054/brst.2001.0311. [DOI:10.1054/brst.2001.0311]
28. Shughrue PJ, Lane MV, Merchenthaler I. Regulation of progesterone receptor messenger ribonucleic acid in the rat medial preoptic nucleus by estrogenic and antiestrogenic compounds: an in situ hybridization study. Endocrinology. 1997; 138(12): 5476-5484. [DOI:10.1210/endo.138.12.5595]
29. Fink G, Sumner BE, Rosie R, Grace O, Quinn JP. Estrogen control of central neurotransmission: effect on mood, mental state, and memory. [Review]. Cell Mol Neurobiol. (1996; 16(3): 325-344. [DOI:10.1007/BF02088099]
30. Kretz O, Fester L, Wehrenberg U, Zhou L, Brauckmann S, Zhao S, Rune GM. Hippocampal synapses depend on hippocampal estrogen synthesis. J Neurosci. 2004; 24(26): 5913-5921. [DOI:10.1523/JNEUROSCI.5186-03.2004]
31. Maki PM. Hormone therapy and cognitive function: is there a critical period for benefit? [Review]. Neuroscience. 2006; 138(3): 1027-1030. DOI:10.1016/j.neuroscience.2006.01.001. [DOI:10.1016/j.neuroscience.2006.01.001]
32. Abdelgadir SE, Resko JA, Ojeda SR, Lephart ED, McPhaul MJ, Roselli CE. Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in rat brain. Endocrinology. 1994; 135(1): 395-401. DOI:10.1210/endo.135.1.8013375. [DOI:10.1210/endo.135.1.8013375]
33. Wehrenberg U, Prange-Kiel J, & Rune GM. Steroidogenic factor-1 expression in marmoset and rat hippocampus: co-localization with StAR and aromatase. J Neurochem. 2001; 76(6): 1879-1886. [DOI:10.1046/j.1471-4159.2001.00207.x]
34. Garcia-Segura LM, Wozniak A, Azcoitia I, Rodriguez JR, Hutchison RE, Hutchison JB. Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience. 1999; 89(2): 567-578. [DOI:10.1016/S0306-4522(98)00340-6]
35. Azcoitia I, Sierra A, Veiga S, Honda S, Harada N, Garcia-Segura LM. Brain aromatase is neuroprotective. J Neurobiol. 2001; 47(4): 318-329. [DOI:10.1002/neu.1038]
36. Prange-Kiel J, Wehrenberg U, Jarry H, Rune GM. Para/autocrine regulation of estrogen receptors in hippocampal neurons. Hippocampus. 2003; 13(2): 226-234. [DOI:10.1002/hipo.10075]
37. Baydas G, Ozveren F, Tuzcu M, Yasar A. Effects of thinner exposure on the expression pattern of neural cell adhesion molecules, level of lipid peroxidation in the brain and cognitive function in rats. Eur J Pharmacol. 2005; 512(3): 181-187. [DOI:10.1016/j.ejphar.2005.02.038]
38. Murase S, Schuman EM. The role of cell adhesion molecules in synaptic plasticity and memory. [Review]. Curr Opin Cell Biol. 1999; 11(5): 549-553. [DOI:10.1016/S0955-0674(99)00019-8]
39. Heikkinen T, Puolivali J, Liu L, Rissanen A, Tanila H. Effects of ovariectomy and estrogen treatment on learning and hippocampal neurotransmitters in mice. Horm Behav. 2002; 41(1): 22-32. [DOI:10.1006/hbeh.2001.1738]
40. Rossetti ZL, Carboni S. Noradrenaline and dopamine elevations in the rat prefrontal cortex in spatial working memory. J Neurosci. 2005; 25(9): 2322-2329. DOI: 10.1523/JNEUROSCI.3038-04.2005. [DOI:10.1523/JNEUROSCI.3038-04.2005]
41. Vierk R, Glassmeier G, Zhou L, Brandt N, Fester L, Dudzinski D, Rune GM. Aromatase inhibition abolishes LTP generation in female but not in male mice. J Neurosci. 2012; 32(24): 8116-8126. [DOI:10.1523/JNEUROSCI.5319-11.2012]
42. Zhou L, Fester L, von Blittersdorff B, Hassu B, Nogens H, Prange-Kiel J, Rune GM. Aromatase inhibitors induce spine synapse loss in the hippocampus of ovariectomized mice. Endocrinology. 2010; 151(3): 1153-1160. doi: 10.1210/en.2009-0254. [DOI:10.1210/en.2009-0254]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2007 All Rights Reserved | Medical Laboratory Journal

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.