Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-22T23:22:05.512Z Has data issue: false hasContentIssue false
  • English
  • Français

Long-term effects of ageing and ovariectomy on aversive and recognition memory and DNA damage in the hippocampus of female rats

Published online by Cambridge University Press:  08 October 2013

Daniela Dimer Leffa ,
Adriani Paganini Damiani ,
Daiane Dal Col Damazio ,
Naiana Pereira Guerra ,
Morgana Moretti ,
Geovana Gomes da Silva de Brito ,
Carina Rodrigues Boeck ,
Elaine Cristina Gavioli  and
Vanessa Moraes de Andrade
Daniela Dimer Leffa*
Affiliation:
Laboratory of Molecular and Cellular Biology (LABIM), Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
Adriani Paganini Damiani
Affiliation:
Laboratory of Molecular and Cellular Biology (LABIM), Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
Daiane Dal Col Damazio
Affiliation:
Laboratory of Molecular and Cellular Biology (LABIM), Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
Naiana Pereira Guerra
Affiliation:
Laboratory of Neuroscience, Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
Morgana Moretti
Affiliation:
Laboratory of Neuroscience, Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
Geovana Gomes da Silva de Brito
Affiliation:
Laboratory of Neuroscience, Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
Carina Rodrigues Boeck
Affiliation:
Laboratory of Neuroscience, Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
Elaine Cristina Gavioli
Affiliation:
Laboratory of Behavioural Pharmacology, Postgraduate Programme of Behavioural Neuroscience, Centre for Biosciences, University Campus, Federal University of Rio Grande do Norte, Natal, RN, Brazil
Vanessa Moraes de Andrade
Affiliation:
Laboratory of Molecular and Cellular Biology (LABIM), Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
*
Daniela Dimer Leffa, Laboratory of Molecular and Cellular Biology, Postgraduate Programme of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, 888.06-000, Criciúma, SC, Brazil. Tel: +55 (48) 3431 2757; Fax: +55 (48) 3431 2671; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

This study investigated the influence of ageing – in particular the decrease of gonadal hormone levels during the ageing process – on the memory and the levels of DNA damage in the hippocampus of female rats.

Methods

Three groups of female Wistar rats were investigated: Group I consisted of non-ovariectomised, adult animals (6 months old); Group II consisted of non-ovariectomised, aged animals (18 months old); and Group III consisted of ovariectomised, aged animals (18 months old). The memory of the animals in these groups was examined via novel object recognition and inhibitory avoidance tests. The hippocampus tissue samples of all animals were obtained via biopsy and used to quantify the DNA damage using a Comet Assay.

Results

According to our findings, the process of ageing results in a change during the behavioural tests. To prevent genotoxic damage to the hippocampus caused by the ageing process, lowered hormone levels seem to be part of a protective biochemical mechanism in the body of rats. Animals that were previously submitted to an ovariectomy adapted better to these lower levels of hormones.

Conclusion

Our results indicate that ovariectomy can provide beneficial long-term effects on the memory. However, this could be specific to the kind of memory examined, as the aversive memory deficits caused by ageing were not affected by ovariectomy.

Keywords

agedComet Assayinhibitory avoidance testobject recognition testovariectomy
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 26 , Issue 3 , June 2014 , pp. 161 - 169
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.King, CM, Bristow-Craig, HE, Gillespie, ES, Barnett, YA. In vivo antioxidant status, DNA damage, mutation and DNA repair capacity in cultured lymphocytes from healthy 75- to 80-year-old humans. Mutat Res 1997;377:137–147.CrossRefGoogle ScholarPubMed
2.Masoro, EJ. Dietary restriction and aging. J Am Geriatr Soc 1993;41:994–999.CrossRefGoogle ScholarPubMed
3.Sohal, RS, Dubey, A. Mitochondrial oxidative damage, hydrogen peroxide release, and aging. Free Radic Biol Med 1994;16:621–626.CrossRefGoogle ScholarPubMed
4.Ivancsits, S, Diem, E, Jahn, O, Rüdiger, HW. Age-related effects on induction of DNA strand breaks by intermittent exposure to electromagnetic fields. Mech Ageing Dev 2003;124:847–850.CrossRefGoogle ScholarPubMed
5.Kankofer, M, Radzki, RP, Bieńko, M, Albera, E. Anti-oxidative/oxidative status of rat liver after ovariectomy. J Vet Med A Physiol Pathol Clin Med 2007;54:225–229.CrossRefGoogle ScholarPubMed
6.Pilšáková, L, Riečanský, I, Jagla, F. The physiological actions of isoflavone phytoestrogens. Physiol Res 2010;59:651–664.CrossRefGoogle ScholarPubMed
7.Greendale, GA, Lee, NP, Arriola, ER. The menopause. Lancet 1999;353:571–580.CrossRefGoogle ScholarPubMed
8.Sugioka, K, Shimosegawa, Y, Nakano, M. Estrogens as natural antioxidants of membrane phospholipid peroxidation. FEBS Lett 1987;210:37–39.CrossRefGoogle ScholarPubMed
9.Green, PS, Gordon, K, Simpkins, JW. Phenolic A ring requirement for the neuroprotective effects of steroids. J Steroid Biochem Mol Biol 1997;63:229–235.CrossRefGoogle ScholarPubMed
10.Luine, VN. Sex steroids and cognitive function. J Neuroendocrinol 2008;20:866–872.CrossRefGoogle ScholarPubMed
11.Persky, AM, Green, PS, Stubley, Let al. Protective effect of estrogens against oxidative damage to heart and skeletal muscle in vivo and in vitro. Proc Soc Exp Biol Med 2000;223:59–66.Google ScholarPubMed
12.Gibbs, RB, Gabor, R, Cox, T, Johnson, DA. Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat. Psychoneuroendocrinology 2004;29:741–748.CrossRefGoogle ScholarPubMed
13.Luine, VN, Jacome, LF, Maclusky, NJ. Rapid enhancement of visual and place memory by estrogens in rats. Endocrinology 2003;144:2836–2844.CrossRefGoogle ScholarPubMed
14.Rhodes, ME, Frye, CA. Androgens in the hippocampus can alter, and be altered by, ictal activity. Pharmacol Biochem Behav 2004;78:483–493.CrossRefGoogle ScholarPubMed
15.Robertson, MC, Owens, RE, Klindt, J, Friesen, HG. Ovariectomy leads to a rapid increase in rat placental lactogen secretion. Endocrinology 1984;114:1805–1811.CrossRefGoogle ScholarPubMed
16.Marcondes, FK, Bianchi, FJ, Tanno, AP. Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol 2002;62:609–614.CrossRefGoogle ScholarPubMed
17.Marcondes, FK, Miguel, KJ, Melo, LL, Spadari-Bratfisch, RC. Estrous cycle influences the response of female rats in the elevated plus-maze test. Physiol Behav 2001;74:435–440.CrossRefGoogle ScholarPubMed
18.Zuluaga, MJ, Agrati, D, Pereira, M, Uriarte, N, Fernández-Guasti, A, Ferreira, A. Experimental anxiety in the black and white model in cycling, pregnant and lactating rats. Physiol Behav 2005;84:279–286.CrossRefGoogle ScholarPubMed
19.de Chaves, G, Moretti, M, Castro, AAet al. Effects of long-term ovariectomy on anxiety and behavioral despair in rats. Physiol Behav 2009;97:420–425.CrossRefGoogle ScholarPubMed
20.Réus, GZ, Valvassori, SS, Machado, RA, Martins, MR, Gavioli, EC, Quevedo, J. Acute treatment with low doses of memantine does not impair aversive, non-associative and recognition memory in rats. Naunyn Schmiedebergs Arch Pharmacol 2008;376:295–300.CrossRefGoogle Scholar
21.Roesler, R, Vianna, MR, de-Paris, F, Quevedo, J. Memory-enhancing treatments do not reverse the impairment of inhibitory avoidance retention induced by NMDA receptor blockade. Neurobiol Learn Mem 1999;72:252–258.CrossRefGoogle Scholar
22.Izquierdo, I, Medina, JH. Memory formation: the sequence of biochemical events in the hippocampus and its connection to activity in other brain structures. Neurobiol Learn Mem 1997;68:285–316.CrossRefGoogle ScholarPubMed
23.Singh, NP, McCoy, MT, Tice, RR, Schneider, EL. A simple technique for quantization of low levels of DNA damage in individual cells. Exp Cell Res 1988;175:184–191.CrossRefGoogle Scholar
24.Tice, RR, Agurell, E, Anderson, Det al. Single cell gel/Comet Assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 2000;35:206–221.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
25.Collins, AR. The Comet Assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 2004;26:249–261.CrossRefGoogle ScholarPubMed
26.Luparini, MR, Del Vecchio, A, Barillari, G, Magnani, M, Prosdocimi, M. Cognitive impairment in old rats: a comparison of object displacement, object recognition and water maze. Aging (Milano) 2000;12:264–273.Google ScholarPubMed
27.Martinez, JL Jr, Rigter, H. Assessment of retention capacities in old rats. Behav Neural Biol 1983;39:181–191.CrossRefGoogle ScholarPubMed
28.Vannucchi, MG, Scali, C, Kopf, SR, Pepeu, G, Casamenti, F. Selective muscarinic antagonists differentially affect in vivo acetylcholine release and memory performances of young and aged rats. Neuroscience 1997;79:837–846.CrossRefGoogle Scholar
29.Winocur, G, Hasher, L. Aging and time-of-day effects on cognition in rats. Behav Neurosci 1999;113:991–997.CrossRefGoogle ScholarPubMed
30.Scali, C, Giovannini, MG, Prosperi, C, Bartolini, L, Pepeu, G. Tacrine administration enhances extracellular acetylcholine in vivo and restores the cognitive impairment in aged rats. Pharmacol Res 1997;36:463–469.CrossRefGoogle ScholarPubMed
31.Wallace, M, Frankfurt, M, Arellanos, A, Inagaki, T, Luine, V. Impaired recognition memory and decreased prefrontal cortex spine density in aged female rats. Ann N Y Acad Sci 2007;1097:54–57.CrossRefGoogle ScholarPubMed
32.Lethaby, A, Hogervorst, E, Richards, M, Yesufu, A, Yaffe, K. Hormone replacement therapy for cognitive function in postmenopausal women. Cochrane Database Syst Rev 2008;1:CD003122.Google Scholar
33.Markowska, AL, Savonenko, AV. Effectiveness of estrogen replacement in restoration of cognitive function after long-term estrogen withdrawal in aging rats. J Neurosci 2002;22:10985–10995.CrossRefGoogle ScholarPubMed
34.Monteiro, SC, de Mattos, CB, Ben, J, Netto, CA, Wyse, AT. Ovariectomy impairs spatial memory: prevention and reversal by a soy isoflavone diet. Metab Brain Dis 2008;23:243–253.CrossRefGoogle ScholarPubMed
35.Wallace, M, Luine, V, Arellanos, A, Frankfurt, M. Ovariectomized rats show decreased recognition memory and spine density in the hippocampus and prefrontal cortex. Brain Res 2006;1126:176–182.CrossRefGoogle ScholarPubMed
36.Bimonte-Nelson, HA, Singleton, RS, Hunter, CL, Price, KL, Moore, AB, Granholm, AC. Ovarian hormones and cognition in the aged female rat: I. Long-term, but not short-term, ovariectomy enhances spatial performance. Behav Neurosci 2003;117:1395–1406.CrossRefGoogle Scholar
37.Pan, M, Li, Z, Yeung, V, Xu, RJ. Dietary supplementation of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene expression of BDNF, TrkB receptor and synaptic factors in ovariectomized rats. Nutr Metab (Lond) 2010;15:7–75.Google Scholar
38.Lacreuse, A, Herndon, JG, Moss, MB. Cognitive function in aged ovariectomized female rhesus monkeys. Behav Neurosci 2000;114:506–513.CrossRefGoogle ScholarPubMed
39.Heikkinen, T, Puoliväli, J, Tanila, H. Effects of long-term ovariectomy and estrogen treatment on maze learning in aged mice. Exp Gerontol 2004;39:1277–1283.CrossRefGoogle ScholarPubMed
40.Bimonte-Nelson, HA, Singleton, RS, Williams, BJ, Granholm, AC. Ovarian hormones and cognition in the aged female rat: II. Progesterone supplementation reverses the cognitive enhancing effects of ovariectomy. Behav Neurosci 2004;118:707–714.CrossRefGoogle ScholarPubMed
41.Bimonte-Nelson, HA, Francis, KR, Umphlet, CD, Granholm, AC. Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats. Eur J Neurosci 2006;24:229–242.CrossRefGoogle ScholarPubMed
42.Hua, F, Reiss, JI, Tang, Het al. Progesterone and low-dose vitamin D hormone treatment enhances sparing of memory following traumatic brain injury. Horm Behav 2012;61:642–651.CrossRefGoogle ScholarPubMed
43.Singh, NP, Danner, DB, Tice, RRet al. Basal DNA damage in individual human lymphocytes with age. Mutat Res 1991;256:1–6.CrossRefGoogle ScholarPubMed
44.Heuser, VD, da Silva, J, Moriske, HJ, Dias, JF, Yoneama, ML, de Freitas, TR. Genotoxicity biomonitoring in regions exposed to vehicle emissions using the Comet Assay and the micronucleus test in native rodent Ctenomys minutus. Environ Mol Mutagen 2002;40:227–235.CrossRefGoogle ScholarPubMed
45.Chevanne, M, Caldini, R, Tombaccini, D, Mocali, A, Gori, G, Paoletti, F. Comparative levels of DNA breaks and sensitivity to oxidative stress in aged and senescent human fibroblasts: a distinctive pattern for centenarians. Biogerontology 2003;4:97–104.CrossRefGoogle ScholarPubMed
46.López-Diazguerrero, NE, Luna-López, A, Gutiérrez-Ruiz, MC, Zentella, A, Königsberg, M. Susceptibility of DNA to oxidative stressors in young and aging mice. Life Sci 2005;77:2840–2854.CrossRefGoogle Scholar
47.Rossi, DJ, Seita, J, Czechowicz, A, Bhattacharya, D, Bryder, D, Weissman, IL. Hematopoietic stem cell quiescence attenuates DNA damage response and permits DNA damage accumulation during aging. Cell Cycle 2007;6:2371–2376.CrossRefGoogle ScholarPubMed
48.Heuser, VD, de Andrade, VM, Peres, A, Gomes de Macedo Braga, LM, Bogo Chies, JA. Influence of age and sex on spontaneous DNA damage detected by micronucleus test and Comet Assay the peripheral blood cells of mice. Cell Biol Int 2008;32:1223–1229.CrossRefGoogle Scholar
49.Schumacher, M, Coirini, H, McEwen, BS. Regulation of high-affinity GABAA receptors in the dorsal hippocampus by estradiol and progesterone. Brain Res 1989;487:178–183.CrossRefGoogle ScholarPubMed
50.Bossé, R, DiPaolo, T. The modulation of brain dopamine and GABAA receptors by estradiol: a clue for CNS changes occurring at menopause. Cell Mol Neurobiol 1996;16:199–212.CrossRefGoogle ScholarPubMed
51.Tominaga, K, Yamauchi, A, Shuto, Het al. Ovariectomy aggravates convulsions and hippocampal gamma-aminobutyric acid inhibition induced by cyclosporin A in rats. Eur J Pharmacol 2001;430:243–249.CrossRefGoogle ScholarPubMed
52.Verma, Y, Rana, SV. Modulation of phase-II enzyme activities in benzene treated ovariectomized rats. Environ Toxicol Pharmacol 2011;31:371–377.CrossRefGoogle ScholarPubMed
53.Andersen, ML, Ribeiro, DA, Alvarenga, TAet al. Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats? Horm Behav 2010;57:216–221.CrossRefGoogle ScholarPubMed