Voluntary exercise and estrogen replacement ameliorate the impairment of fear memory and decrease in the number of neurons in the hippocampus induced by ovariectomy in rats

authors:

avatar A. li Rashidy-Pour , * , avatar Abbas Ali Vafaei , avatar Kowsar Bavarsad , avatar Saeed Haghighi

Koomesh: Vol.19, issue 3; 655-665
published online: August 02, 2017
article type: Research Article
received: September 01, 2016
accepted: April 02, 2017

how to cite: Rashidy-Pour A L, Vafaei A A, Bavarsad K, Haghighi S. Voluntary exercise and estrogen replacement ameliorate the impairment of fear memory and decrease in the number of neurons in the hippocampus induced by ovariectomy in rats. koomesh. 2017;19(3):e152912. 

Abstract

Introduction: Previous studies indicated that the exercise has beneficial effects on cognitive activities and ovariectomies causes the impairment of learning and memory. The aim of this study was to determine the influence of voluntary exercise and estrogen replacement on the effects of ovariectomy on fear memory and hippocampal neuron number in rat. Materials and Methods: In this experimental study, adult female Wistar rat (180-220 gr) were used. One week after ovariectomy, the rats received ß-Stradiol (estrogen 20 µg/kg) or vehicle (2ml/kg) daily and were allowed to freely exercise in a running wheel for 2 weeks. After this period, their learning and memory were trained and tested on a passive avoidance task that succeeded by a retention test two days later. Then, all animal were decapitated, and their hippocampi were removed. The number of neurons was counted in different regions of hippocampus. Results: Analysis of data indicated that the ovariectomy impaired the fear memory and decreased the number of neurons in the hippocmpaus. Volunatry exercise or exstrogen replacement alone, and together improved the deficits in fear memory and neuron counting induced by ovariectomy Conclusion: Voluntary exercise and estrogen have benfical effects on cognitive deficits associated with the reduction of female sex hormones such as seen in post-monpouse woman.

References

  • 1.

    Akhavan MM, Miladi-Gorji H, Emami-Abarghoie M, Safari M, Sadighi-Moghaddam B, Vafaei AA, Rashidy-Pour A. Maternal voluntary exercise during pregnancy enhances the spatial learning acquisition but not the retention of memory in rat pups via a TrkB-mediated mechanism: the role of hippocampal BDNF Expression. Iran J Basic Med Sci 2013; 16: 955.

  • 2.

    van Praag H. Neurogenesis and exercise: past and future directions. Neuromolecular Med 2008; 10: 128-140.

  • 3.

    Grealy MA, Johnson DA, Rushton SK. Improving cognitive function after brain injury: the use of exercise and virtual reality. Arch Phys Med Rehabil 1999; 80: 661-667.

  • 4.

    Ghaffari Z, Vafaei AA, Rashidy-Pour A, Hadjzadeh MAR, Hosseini SM. Effects of maternal hypothroidism during preganacy on anxiety-like behaviors in adulthood rats: Impact of moderate treadmill exercise. Koomesh 2016; 17: 707-717. (Persian).

  • 5.

    Ivy AS, Rodriguez FG, Garcia C, Chen MJ, Russo-Neustadt AA. Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant. Pharmacol Biochem Behav 2003; 75: 81-88.

  • 6.

    Carro E, Trejo JL, Busiguina S, Torres-Aleman I. Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci 2001; 21: 5678-5684.

  • 7.

    Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, et al. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci 2003; 18: 2803-2812.

  • 8.

    Sutoo D, Akiyama K. Regulation of brain function by exercise. Neurobiol Dis 2003; 13: 1-14.

  • 9.

    Tanehkar F, Rashidy-Pour A, Vafaei AA, Sameni HR, Haghighi S, Miladi-Gorji H, et al. Voluntary exercise does not ameliorate spatial learning and memory deficits induced by chronic administration of nandrolone decanoate in rats. Horm Behav 2013; 63: 158-165.

  • 10.

    van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A 1999; 96: 13427-13431.

  • 11.

    Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR. Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 2004; 124: 71-79.

  • 12.

    van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999; 2: 266-270.

  • 13.

    Kim SH, Kim HB, Jang MH, Lim BV, Kim YJ, Kim YP, Kim SS, et al. Treadmill exercise increases cell proliferation without altering of apoptosis in dentate gyrus of Sprague-Dawley rats. Life Sci 2002; 71: 1331-1340.

  • 14.

    Hojo Y, Murakami G, Mukai H, Higo S, Hatanaka Y, Ogiue-Ikeda M, et al. Estrogen synthesis in the brain--role in synaptic plasticity and memory. Mol Cell Endocrinol 2008; 290: 31-43.

  • 15.

    Mukai H, Takata N, Ishii HT, Tanabe N, Hojo Y, Furukawa A, et al. Hippocampal synthesis of estrogens and androgens which are paracrine modulators of synaptic plasticity: synaptocrinology. Neuroscience 2006; 138: 757-764.

  • 16.

    Murakami G, Tsurugizawa T, Hatanaka Y, Komatsuzaki Y, Tanabe N, Mukai H, et al. Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus. Biochem Biophys Res Commun 2006; 351: 553-558.

  • 17.

    Stephens C, Pachana NA, Bristow V. The effect of hormone replacement therapy on mood and everyday memory in younger mid-life women. Psychol Health Med 2006; 11: 461-469.

  • 18.

    Harburger LL, Bennett JC, Frick KM. Effects of estrogen and progesterone on spatial memory consolidation in aged females. Neurobiol Aging 2007; 28: 602-610.

  • 19.

    Bohacek J, Daniel JM. Increased daily handling of ovariectomized rats enhances performance on a radial-maze task and obscures effects of estradiol replacement. Horm Behav 2007; 52: 237-243.

  • 20.

    Slaven L, Lee C. Mood and symptom reporting among middle-aged women: the relationship between menopausal status, hormone replacement therapy, and exercise participation. Health psychol 1997; 16: 203-208.

  • 21.

    Aiello EJ, Yasui Y, Tworoger SS, Ulrich CM, Irwin ML, Bowen D, et al. Effect of a yearlong, moderate-intensity exercise intervention on the occurrence and severity of menopause symptoms in postmenopausal women. Menopause 2004; 11: 382-388.

  • 22.

    Shangold MM. Exercise in the menopausal woman. Obstet Gynecol 1990; 75: 53S-58S.

  • 23.

    Brown BS, Payne T, Kim C, Moore G, Krebs P, Martin W. Chronic response of rat brain norepinephrine and serotonin levels to endurance training. J Appl Physiol Respir Environ Exerc Physiol 1979; 46: 19-23.

  • 24.

    Ormerod BK, Lee TT, Galea LA. Estradiol enhances neurogenesis in the dentate gyri of adult male meadow voles by increasing the survival of young granule neurons. Neuroscience 2004; 128: 645-654.

  • 25.

    Tanapat P, Hastings NB, Reeves AJ, Gould E. Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 1999; 19: 5792-5801.

  • 26.

    McLaughlin KJ, Bimonte-Nelson H, Neisewander JL, Conrad CD. Assessment of estradiol influence on spatial tasks and hippocampal CA1 spines: Evidence that the duration of hormone deprivation after ovariectomy compromises 17-estradiol effectiveness in altering CA1 spines. Horm Behav 2008; 54: 386-395.

  • 27.

    Shuster LT, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA. Premature menopause or early menopause: long-term health consequences. Maturitas 2010; 65: 161-166.

  • 28.

    Banasr M, Hery M, Brezun JM, Daszuta A. Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus. Eur J Neurosci 2001; 14: 1417-1424.

  • 29.

    Rashidy-Pour A, Vafaei AA, Taherian AA, Miladi-Gorji H, Sadeghi H, Fathollahi Y, Bandegi AR. Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval of long-term memory in rats. Behav Brain Res 2009; 203: 76-80.

  • 30.

    Ebrahimi S, Rashidy-Pour A, Vafaei AA, Akhavan MM, Haghighi S. Influence of basolateral amygdala lesion on the inhibitory effects of propranolol on voluntary exercise- induced enhancement of learning and memory. Koomesh 2010; 11: 145-153. (Persian).

  • 31.

    Shafiee SM, Vafaei AA, Rashidy-Pour A. Effects of maternal hypothyroidism during pregnancy on learning, memory and hippocampal BDNF in rat pups: Beneficial effects of exercise. Neuroscience 2016; 329: 151-161.

  • 32.

    Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002; 25: 295-301.

  • 33.

    Kim BK, Seo JH. Treadmill exercise alleviates post-traumatic stress disorder-induced impairment of spatial learning memory in rats. J Exerc Rehabil 2013; 9: 413-419.

  • 34.

    Ben J, Soares FM, Scherer EB, Cechetti F, Netto CA, Wyse AT. Running exercise effects on spatial and avoidance tasks in ovariectomized rats. Neurobiol Learn Mem 2010; 94: 312-317.

  • 35.

    Wise PM. Estrogens and neuroprotection. Trends Endocrinol Metab 2002; 13: 229-230.

  • 36.

    van Duijn CM. Hormone replacement therapy and Alzheimer's disease. Maturitas 1999; 31: 201-205.

  • 37.

    Green PS, Simpkins JW. Neuroprotective effects of estrogens: potential mechanisms of action. Int J Dev Neurosci 2000; 18: 347-358.

  • 38.

    Monteiro SC, Matt C, Bavaresco CS, Netto CA, Wyse AT. Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze. Neurobiol Learn Mem 2005; 84: 192-199.

  • 39.

    van Praag H. Exercise and the brain: something to chew on. Trends Neurosci 2009; 32: 283-290.

  • 40.

    Jin J, Jing H, Choi G, Oh MS, Ryu JH, Jeong JW, et al. Voluntary exercise increases the new cell formation in the hippocampus of ovariectomized mice. Neurosci Lett 2008; 439: 260-263.

  • 41.

    Wu CW, Chen YC, Yu L, Chen HI, Jen CJ, Huang AM, et al. Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory. J Neurochem 2007; 103: 2471-2481.

  • 42.

    Hillman CH, Erickson KI, Kramer AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 2008; 9: 58-65.

  • 43.

    Sherwin BB. Estrogen and cognitive functioning in women: lessons we have learned. Behav Neurosci 2012; 126: 123.

  • 44.

    Gonzlez-Burgos I, Alejandre-Gmez M, Cervantes M. Spine-type densities of hippocampal CA1 neurons vary in proestrus and estrus rats. Neurosci Lett 2005; 379: 52-54.

  • 45.

    Frick KM. Estrogens and age-related memory decline in rodents: what have we learned and where do we go from here? Horm Behav 2009; 55: 2-23.

  • 46.

    Fan L, Zhao Z, Orr PT, Chambers CH, Lewis MC, Frick KM. Estradiol-induced object memory consolidation in middle-aged female mice requires dorsal hippocampal extracellular signal-regulated kinase and phosphatidylinositol 3-kinase activation. J Neurosci 2010; 30: 4390-4400.

  • 47.

    McEwen BS, Alves SE. Estrogen actions in the central nervous system 1. Endocr Rev 1999; 20: 279-307.

  • 48.

    Shughrue P, Scrimo P, Lane M, Askew R, Merchenthaler I. The distribution of estrogen receptor- mRNA in forebrain regions of the estrogen receptor- knockout mouse. Endocrinology 1997; 138: 5649-5652.

  • 49.

    Walter P, Green S, Greene G, Krust A, Bornert JM, Jeltsch JM, et al. Cloning of the human estrogen receptor cDNA. Proc Natl Acad Sci U S A 1985; 82: 7889-7893.

  • 50.

    Laflamme N, Nappi RE, Drolet G, Labrie C, Rivest S. Expression and neuropeptidergic characterization of estrogen receptors (ERa and ERb) throughout the rat brain: anatomical evidence of distinct roles of each subtype. J Neurobiol 1998; 36: 357-378.

  • 51.

    Tang AC, Nakazawa M, Romeo RD, Reeb BC, Sisti H, McEwen BS. Effects of long-term estrogen replacement on social investigation and social memory in ovariectomized C57BL/6 mice. Horm Behav 2005; 47: 350-357.

  • 52.

    Choleris E, Kavaliers M, Pfaff D. Functional genomics of social recognition. J Neuroendocrinol 2004; 16: 383-389.

  • 53.

    Akama KT, McEwen BS. Estrogen stimulates postsynaptic density-95 rapid protein synthesis via the Akt/protein kinase B pathway. J Neurosci 2003; 23: 2333-2339.

  • 54.

    MacLusky NJ, Luine VN, Hajszan T, Leranth C. The 17alpha and 17beta isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats. Endocrinology 2005; 146: 287-293.

  • 55.

    Woolley CS, McEwen BS. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 1993; 336: 293-306.

  • 56.

    Garcia-Segura LM, Arvalo MA, Azcoitia I. Interactions of estradiol and insulin-like growth factor-I signalling in the nervous system: new advances. Prog Brain Res 2010; 181: 251-272.

  • 57.

    Wang JM, Liu L, Brinton RD. Estradiol-17-induced human neural progenitor cell proliferation is mediated by an estrogen receptor -phosphorylated extracellularly regulated kinase pathway. Endocrinology 2008; 149: 208-218.##.