Skip to main content
SpringerLink
Log in

Chronic (3-Weeks) Treatment of Estrogen (17β-Estradiol) Enhances Working and Reference Memory in Ovariectomized Rats: Role of Acetylcholine

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Recently there has been a growing interest in the effects of estrogen on cognitive functions. In this study, we aimed to examine 17β-estradiol treatment on working and reference memory in ovariectomized rats. We also examined the changes in the acetylcholine (ACh) levels in the brain areas associated with learning and memory. The study was performed on Sprague–Dawley type 3-month-old female rats. The rats were divided into four groups as control, ovariectomy (OVX), and OVX and estrogen treatment (10 µg/day i.p. 17β-estradiol) groups for 3 (OVX + E3) and 21 days OVX + E21). The rats were trained on eight arm radial maze task with eight arms baited to assess spatial memory, in addition four arms baited to assess both working and reference memory performances. The electron microscope images of the ACh vesicles in the frontal cortex, temporal cortex and hippocampus areas of the brain which are important regions for learning and memory were screened. Results showed that long term 17β-estradiol treatment has positive effects on both reference memory and working memory and that ACh vesicles increased in the examined brain areas, especially in hippocampus. Our results suggest that 3 weeks 17β-estradiol treatment may have an ameliorative effect on the memory through the central cholinergic system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Naulé L, Picot M, Martini M, Parmentier C, Hardin-Pouzet H, Keller M, Franceschini I, Mhaouty-Kodja S (2014) Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice. J Endocrinol 220:375–388

    Article  PubMed  Google Scholar 

  2. Hara Y, Waters EM, McEwen BS, Morrison JH (2015) Estrogen effects on cognitive and synaptic health over the life course. Physiol Rev 95:785–807

    Article  CAS  PubMed  Google Scholar 

  3. Luine VN (2008) Sex steroids and cognitive function. J Neuroendocrinol 20:866–872

    Article  CAS  PubMed  Google Scholar 

  4. Norbury R, Travis MJ, Erlandsson K, Waddington W, Ell PJ, Murphy DG (2007) Estrogen therapy and brain muscarinic receptor density in healthy females: a SPET study. Horm Behav 51:249–257

    Article  CAS  PubMed  Google Scholar 

  5. Leranth C, Shanabrough M, Horvath TL (2000) Hormonal regulation of hippocampal spine synapse density involves subcortical mediation. Neuroscience 101:349–356

    Article  CAS  PubMed  Google Scholar 

  6. Pompili A, Tomaz C, Arnone B, Tavares MC, Gasbarri A (2010) Working and reference memory across the estrous cycle of rat: a long-term study in gonadally intact females. Behav Brain Res 213:10–18

    Article  PubMed  Google Scholar 

  7. Daniel JM, Fader AJ, Al Spencer, Dohanich GP (1997) Estrogen enhances performance of female rats during acquisition of a radial arm maze task. Horm Behav 32:217–225

    Article  CAS  PubMed  Google Scholar 

  8. Fillit H, Luine V (1997) The neurobiology of gonadal hormones and cognitive decline in late life. Maturitas 26:159–164

    Article  CAS  PubMed  Google Scholar 

  9. Luine VN (1985) Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats. Exp Neurol 89:484–490

    Article  CAS  PubMed  Google Scholar 

  10. Daniel JM, Hulst JL, Lee CD (2005) Role of hippocampal M2 muscarinic receptors in the estrogen-induced enhancement of working memory. Neuroscience 132:57–64

    Article  CAS  PubMed  Google Scholar 

  11. Qu N, Wang L, Liu ZC, Tian Q, Zhang Q (2013) Oestrogen receptor α agonist improved long-term ovariectomy-induced spatial cognition deficit in young rats. Int J Neuropsychopharmacol 16:1071–1082

    Article  CAS  PubMed  Google Scholar 

  12. Alonso A, González-Pardo H, Garrido P, Conejo NM, Llaneza P, Díaz F, Del Rey CG, González C (2010) Acute effects of 17 β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats. Age (Dordr) 32:421–434

    Article  CAS  Google Scholar 

  13. Wang VC, Neese SL, Korol DL, Schantz SL (2009) Chronic estradiol replacement impairs performance on an operant delayed spatial alternation task in young, middle-aged, and old rats. Horm Behav 56:382–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. King R, Travers C, O’Neil S, Byrne G, Khoo SK (2004) The influence of postmenopausal hormone replacement therapy on cognitive functioning: results from an observational study. J Br Menopause Soc 10:103–107

    Article  PubMed  Google Scholar 

  15. Fader AJ, Johnson EM, Dohanich GP (1999) Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine on a radial-arm maze. Pharmacol Biochem Behav 62:711–717

    Article  CAS  PubMed  Google Scholar 

  16. Squire LR, Stark CE, Clark RE (2004) The medial temporal lobe. Annu Rev Neurosci 27:279–306

    Article  CAS  PubMed  Google Scholar 

  17. Barense MD, Bussey TJ, Lee AC, Rogers TT, Davies RR, Saksida LM, Murray EA, Graham KS (2005) Functional specialization in the human medial temporal lobe. J Neurosci 25:10239–10246

    Article  CAS  PubMed  Google Scholar 

  18. Saksida LM, Bussey TJ, Buckmaster CA, Murray EA (2006) No effect of hippocampal lesions on perirhinal cortex-dependent feature-ambiguous visual discriminations. Hippocampus 16:421–430

    Article  PubMed  Google Scholar 

  19. Waynfort HB, Flecknell PA (1994) Ovariectomy in experimental and surgical technique in the rat, 2nd edn. Academic, Cambridge, pp 276–278

    Google Scholar 

  20. Jacome LF, Gautreaux C, Inagaki T, Mohan G, Alves S, Lubbers LS, Luine V (2010) Estradiol and ERβ agonists enhance recognition memory, and DPN, an ERβ agonist, alters brain monoamines. Neurobiol Learn Mem 94(4):488–498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Olton DS (1978) Characteristics of spatial memory. In: Hulse SH, Fowler H, Honig WK (eds) Cognitive processes in animal behavior. Lawrence Erlbaum Associates, Hillsdale, pp 341–373

    Google Scholar 

  22. Jarrard LE (1983) Selective hippocampal lesions and behavior: effects of kainic acid lesions on performance of place and cue tasks. Behav Neurosci 97:873–889

    Article  CAS  PubMed  Google Scholar 

  23. Shinomiya K, Tokunaga S, Shigemoto Y, Kamei C (2005) Effect of seed coat extract from black soybeans on radial maze performance in rats. Clin Exp Pharmacol Physiol 32:757–760

    Article  CAS  PubMed  Google Scholar 

  24. Uzum G, Díler AS, Bahcekapili N, Tasyüreklí M, Zíylan YZ (2004) Nicotine improves learning and memory in rats: morphological evidence for acetylcholine involvement. Int J Neurosci 114:1163–1179

    Article  CAS  PubMed  Google Scholar 

  25. Isik H, Sezgin E, Avunduk MC (2010) A new software program for pathological data analysis. Comput Biol Med 40:715–722

    Article  PubMed  Google Scholar 

  26. Savonenko AV, Markowska AL (2003) The cognitive effects of ovariectomy and estrogen replacement are modulated by aging. Neuroscience 119:821–830

    Article  CAS  PubMed  Google Scholar 

  27. Davis DM, Jacobson TK, Aliakbari S, Mizumori SJ (2005) Differential effects of estrogen on hippocampal- and striatal-dependent learning. Neurobiol Learn Mem 84:132–137

    Article  CAS  PubMed  Google Scholar 

  28. Hruska Z, Dohanich GP (2007) The effects of chronic estradiol treatment on working memory deficits induced by combined infusion of beta-amyloid (1–42) and ibotenic acid. Horm Behav 52:297–306

    Article  CAS  PubMed  Google Scholar 

  29. Galea LA, Wide JK, Paine TA, Holmes MM, Ormerod BK, Floresco SB (2001) High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory. Behav Brain Res 126:115–126

    Article  CAS  PubMed  Google Scholar 

  30. Sinopoli KJ, Floresco SB, Galea LA (2006) Systemic and local administration of estradiol into the prefrontal cortex or hippocampus differentially alters working memory. Neurobiol Learn Mem 86:293–304

    Article  CAS  PubMed  Google Scholar 

  31. Luine VN, Richards ST, Wu VY, Beck KD (1998) Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters. Horm Behav 34:149–162

    Article  CAS  PubMed  Google Scholar 

  32. Heikkinen T, Puoliväli J, Liu L, Rissanen A, Tanila H (2002) Effects of ovariectomy and estrogen treatment on learning and hippocampal neurotransmitters in mice. Horm Behav 41:22–32

    Article  CAS  PubMed  Google Scholar 

  33. Gibbs RB (1996) Expression of estrogen receptor-like immunoreactivity by different subgroups of basal forebrain cholinergic neurons in gonadectomized male and female rats. Brain Res 720:61–68

    Article  CAS  PubMed  Google Scholar 

  34. Takuma K, Mizoguchi H, Funatsu Y, Hoshina Y, Himeno Y, Fukuzaki E, Kitahara Y, Arai S, Ibi D, Kamei H, Matsuda T, Koike K, Inoue M, Nagai T, Yamada K (2012) Combination of chronic stress and ovariectomy causes conditioned fear memory deficits and hippocampal cholinergic neuronal loss in mice. Neuroscience 207:261–273

    Article  CAS  PubMed  Google Scholar 

  35. Espinosa-Raya J, Plata-Cruz N, Neri-Gómez T, Camacho-Arroyo I, Picazo O (2011) Effects of short-term hormonal replacement on learning and on basal forebrain ChAT and TrkA content in ovariectomized rats. Brain Res 1375:77–84

    Article  CAS  PubMed  Google Scholar 

  36. Gibbs RB, Nelson D, Hammond R (2014) Role of GPR30 in mediating estradiol effects on acetylcholine release in the hippocampus. Horm Behav 66:339–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Engler-Chiurazzi EB, Talboom JS, Braden BB, Tsang CW, Mennenga S, Andrews M (2012) Continuous estrone treatment impairs spatial memory and does not impact number of basal forebrain cholinergic neurons in the surgically menopausal middle-aged rat. Horm Behav 62:1–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Frick KM, Fernandez SM, Bulinski SC (2002) Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice. Neuroscience 115:547–558

    Article  CAS  PubMed  Google Scholar 

  39. Velázquez-Zamora DA, Garcia-Segura LM, González-Burgos I (2012) Effects of selective estrogen receptor modulators on allocentric working memory performance and on dendritic spines in medial prefrontal cortex pyramidal neurons of ovariectomized rats. Horm Behav 61:512–517

    Article  PubMed  Google Scholar 

  40. Gibbs RB, Chipman AM, Hammond R, Nelson D (2011) Galanthamine plus estradiol treatment enhances cognitive performance in aged ovariectomized rats. Horm Behav 60:607–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chozick BS (1983) The behavioral effects of lesions of the corpus striatum: a review. Int J Neurosci 19:143–159

    Article  CAS  PubMed  Google Scholar 

  42. Ordy JM, Thomas GJ, Volpe BT, Dunlap WP, Colombo PM (1988) An animal model of human-type memory loss based on aging, lesion, forebrain ischemia, and drug studies with the rat. Neurobiol Aging 9:667–683

    Article  CAS  PubMed  Google Scholar 

  43. Barnes CA (1988) Aging and the physiology of spatial memory. Neurobiol Aging 9:563–568

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Gulay Uzum, Nesrin Bahcekapili & Yusuf Ziya Ziylan

  2. Department of Physiology, Faculty of Medicine, Selcuk University, 42075, Konya, Turkey

    Abdulkerim Kasim Baltaci & Rasim Mogulkoc

Authors
  1. Gulay Uzum
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nesrin Bahcekapili
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdulkerim Kasim Baltaci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rasim Mogulkoc
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yusuf Ziya Ziylan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rasim Mogulkoc.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uzum, G., Bahcekapili, N., Baltaci, A.K. et al. Chronic (3-Weeks) Treatment of Estrogen (17β-Estradiol) Enhances Working and Reference Memory in Ovariectomized Rats: Role of Acetylcholine. Neurochem Res 41, 1468–1474 (2016). https://doi.org/10.1007/s11064-016-1858-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-016-1858-4

Keywords

Search

Navigation