Skip to main content

Advertisement

Log in

Effect of Hormone Replacement Therapy in Normalizing Age Related Neuronal Markers in Different Age Groups of Naturally Menopausal Rats

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Aging of the normal brain is accompanied by changes in its structure, function, and metabolism. There are significant gender differences in aging brain. Most of these changes increase during menopausal condition in females when the level of estradiol and progesterone are decreased. The objective of this study was to determine the effect of estradiol and progesterone (separate as well as combined) hormones in neuronal tissues from naturally menopausal rats of different age groups. Results show decreased activity of Acetylcholine esterase (AChE) whereas the level of lipid peroxidation increased with age, and after the hormone treatments both AChE activity and level of lipid peroxidation returned to control values. The deposition of lipofuscin, a pigment that accumulated intraneuronally in brain and other tissues and is considered a marker of aging, was increased with aging and the hormone treatment decreased this deposition. The present study clearly shows reduction in risk factors associated with aging in the murine model system by hormone treatments, namely estrogen and progesterone by increasing the activity of acetylcholine esterase and decreasing the levels of lipid peroxidation and lipofuscin deposition in different parts of aging brain. This study suggests that hormone replacement therapy may either reduce or delay the onset of age related diseases like Alzheimer’s, Parkinson’s and other neurological disorders.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AChE:

acetylcholine esterase

HRT:

hormonal replacement therapy

LP:

lipid peroxide

MDA:

malondialdehyde

References

  • G Alper FK Girgin M Ozgönü G Mentes B Ersöz (1999) ArticleTitleMAO inhibitors and oxidant stress in aging brain tissue Eur Neuropsychopharmacol 19 247–252

    Google Scholar 

  • G Barja Quiroga Particlede R Pérez-Campo M Lopez-Torres (1990) ArticleTitleAnti-oxidant defenses and lipid peroxidation in liver and brain of aged rats Biochem J 272 247–250

    Google Scholar 

  • GJ Boer MH Dozy HBM Uyfings (1984) ArticleTitleCerebellar DNA and tissue water changes in the brain of diabetes insipidus Brattleboro rats are already present at birth Int J Dev Neurosci 2 301–304

    Google Scholar 

  • H Braak (1984) Architectonics as seen by lipofuscin stains A Peters EG Jones (Eds) Cerebral Cortex Plenum Press New York 59–104

    Google Scholar 

  • MM Bradford (1976) ArticleTitleA rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal Biochem 72 248–254 Occurrence Handle10.1016/0003-2697(76)90527-3 Occurrence Handle942051 Occurrence Handle1:CAS:528:DyaE28XksVehtrY%3D

    Article  PubMed  CAS  Google Scholar 

  • F Cand J Verdetti (1989) ArticleTitleSuperoxide dismutase, glutathione peroxidase, catalase and lipid peroxidation in the major organs of the aging rats Free Radic Biol Med 7 59–63 Occurrence Handle10.1016/0891-5849(89)90101-9 Occurrence Handle2753396 Occurrence Handle1:CAS:528:DyaK3MXkt1Kltrw%3D

    Article  PubMed  CAS  Google Scholar 

  • A Das K Kapoor AT Sayeepriyadarshini M Dikshit G Palit C Nath (2000) ArticleTitleImmobilization stress-induced changes in acetylcholinesterase activity and cognitive function in mice Pharmacol Res 42 213–217 Occurrence Handle10.1006/phrs.2000.0678 Occurrence Handle10945925 Occurrence Handle1:CAS:528:DC%2BD3cXls12rtrs%3D

    Article  PubMed  CAS  Google Scholar 

  • P Davies AFJ Maloney (1976) ArticleTitleSelective loss of central cholinergic neurons in Alzheimer’s disease Lancet 2 1403 Occurrence Handle63862 Occurrence Handle1:STN:280:CSiD2sngs1A%3D

    PubMed  CAS  Google Scholar 

  • JA Deutsch (1971) ArticleTitleThe cholinergic synapse and the site of memory Science 74 788–794

    Google Scholar 

  • LM Drach J Bohl HH Goebel (1994) ArticleTitleThe lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer’s disease Dementia 5 234–239 Occurrence Handle7951678 Occurrence Handle1:STN:280:ByqD3sbis1A%3D

    PubMed  CAS  Google Scholar 

  • GL Ellman KD Courtney V Andres SuffixJr RM Feather-stone (1961) ArticleTitleA new and rapid colorimetric determination of acetylcholinesterase activity Biochem Pharmacol 7 88–95 Occurrence Handle10.1016/0006-2952(61)90145-9 Occurrence Handle13726518 Occurrence Handle1:CAS:528:DyaF3MXht1Gns7o%3D

    Article  PubMed  CAS  Google Scholar 

  • A Enz R Amstutz H Boddeke G Gmelin J Malanowski (1993) ArticleTitleBrain selective inhibition of acetylcholinesterase: a novel approach to therapy for Alzheimer’s disease Prog Brain Res 98 431–438 Occurrence Handle8248533 Occurrence Handle1:CAS:528:DyaK2cXksFOjsA%3D%3D

    PubMed  CAS  Google Scholar 

  • A Few R Getty (1967) ArticleTitleOccurrence of lipofuscin as related to aging in the canine and porcine nervous system J Gerontol 22 357–368 Occurrence Handle6028507 Occurrence Handle1:STN:280:CCiC2sjktVI%3D

    PubMed  CAS  Google Scholar 

  • LMG Garcia-Segura I Azcoitia LL DonCarlos (2001) ArticleTitleNeuroprotection by estradiol Prog Neurobiol 63 29–60 Occurrence Handle10.1016/S0301-0082(00)00025-3 Occurrence Handle11040417 Occurrence Handle1:CAS:528:DC%2BD3cXos1Sht7w%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Genisman W Bondareff (1976) ArticleTitleDecrease in the number of synapses in the senescent brain: a quantitative electron microscopic analysis of the dentate gyrus molecular layer in the rat Mech Aging Dev 5 11–23 Occurrence Handle1263605 Occurrence Handle1:STN:280:CSmC2szgs1I%3D

    PubMed  CAS  Google Scholar 

  • M Hagihara I Nishigaki M Maseki K Yagi (1984) ArticleTitleAge-dependent changes in lipid peroxide levels in the lipoprotein fractions of human serum J Gerontol 39 269–272 Occurrence Handle6715802 Occurrence Handle1:CAS:528:DyaL2cXktlKmtLg%3D

    PubMed  CAS  Google Scholar 

  • D Harman (1956) ArticleTitleAging: a theory based on free radical and radiation chemistry J Gerontol 11 298–300 Occurrence Handle13332224 Occurrence Handle1:STN:280:CymD1cvotlU%3D

    PubMed  CAS  Google Scholar 

  • M Inal G Kanbak E Sunal (2001) ArticleTitleAntioxidant enzyme activities and malondialdehyde levels related to aging Clin Chim Acta 305 75–80 Occurrence Handle10.1016/S0009-8981(00)00422-8 Occurrence Handle11249925 Occurrence Handle1:CAS:528:DC%2BD3MXhvVahs74%3D

    Article  PubMed  CAS  Google Scholar 

  • TC James MS Kanungo (1976) ArticleTitleAlterations in atropine sites of the brain of rats as a function of age Biochem Biophys Res Commun 72 170–175 Occurrence Handle10.1016/S0006-291X(76)80057-5 Occurrence Handle985464 Occurrence Handle1:CAS:528:DyaE28XlsVSnt7s%3D

    Article  PubMed  CAS  Google Scholar 

  • HA Johnson S Erner (1972) ArticleTitleNeuron survival in the aging mouse Exp Gerontol 7 111–117 Occurrence Handle10.1016/0531-5565(72)90005-8 Occurrence Handle5042928 Occurrence Handle1:STN:280:CS2B3s3is1M%3D

    Article  PubMed  CAS  Google Scholar 

  • J Kato Y Atsumi M Inaba (1971) ArticleTitleDevelopment of estrogen receptors in the rat hypothalamus J Biochem (Tokyo) 70 1051–1053 Occurrence Handle1:CAS:528:DyaE38XpslCjtA%3D%3D

    CAS  Google Scholar 

  • J Kaur S Singh D Sharma R Singh (2003) ArticleTitleNeurostimulatory and antioxidative effects of l-deprenyl in aged rat brain regions Biogerontology 4 105–111 Occurrence Handle10.1023/A:1023351904840 Occurrence Handle12766535 Occurrence Handle1:CAS:528:DC%2BD3sXivFOiu70%3D

    Article  PubMed  CAS  Google Scholar 

  • JA Kaye C DeCarli JS Luxenberg SI Rapoport (1992) ArticleTitleThe significance of age-related enlargement of the cerebral ventricles in healthy men and women measured by quantitative computed X-ray tomography J Am Geriatric Soc 40 225–231 Occurrence Handle1:STN:280:By2C28nitFc%3D

    CAS  Google Scholar 

  • J Knoll (1988) ArticleTitleThe striatal dopamine dependency of life span in male rats. Longevity study with (-) deprenyl Mech. Aging Dev 46 237–262 Occurrence Handle10.1016/0047-6374(88)90128-5 Occurrence Handle3147347 Occurrence Handle1:CAS:528:DyaL1MXovVOgsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • JF Koster RG Slee (1980) ArticleTitleLipid peroxidation of rat liver microsomes Biochem Biophys Acta 620 489–499 Occurrence Handle6113005 Occurrence Handle1:CAS:528:DyaL3MXkt1Oltg%3D%3D

    PubMed  CAS  Google Scholar 

  • Z Kristofikova O Benesova H Tejkalova (1991) ArticleTitleChanges in water solubility of proteins in aging rat brain Arch Gerontol Geriatr 12 41–48 Occurrence Handle15374463 Occurrence Handle1:STN:280:DC%2BD2cvmtl2lsw%3D%3D Occurrence Handle10.1016/0167-4943(91)90006-C

    Article  PubMed  CAS  Google Scholar 

  • DE Kuhl RA Koeppe S Minoshima SE Snyder EP Ficaro NL Foster KA Frey MR Kilbourn (1999) ArticleTitle In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease Neurology 52 691–699 Occurrence Handle10078712 Occurrence Handle1:CAS:528:DyaK1MXhvFGgsLg%3D

    PubMed  CAS  Google Scholar 

  • M Kurata M Suzuki NS Agar (1993) ArticleTitleAntioxidant systems and erythrocyte life-span in mammals Comp Biochem Physiol 106 477–487 Occurrence Handle1:STN:280:ByuC3cbhtF0%3D

    CAS  Google Scholar 

  • M Lopez-Torres R Perez-Campo C Rojas C Barja Quiroga Particlede (1992) ArticleTitleSensitivity to in vitro lipid peroxidation in liver and brain of aged rats Rev Esp Fisiol 48 191–196 Occurrence Handle1301635 Occurrence Handle1:CAS:528:DyaK3sXnslOqsA%3D%3D

    PubMed  CAS  Google Scholar 

  • OH Lowry NJ Rosebrough AL Farr RJ Randall (1951) ArticleTitleProtein measurement with folin-phenol reagent J Biol Chem 193 265–275 Occurrence Handle14907713 Occurrence Handle1:CAS:528:DyaG38XhsVyrsw%3D%3D

    PubMed  CAS  Google Scholar 

  • T Miura S Muraoka T Ogiso (1996) ArticleTitleLipid peroxidation by estradiol and 2 hydroxyestradiol Steroids 61 379–383 Occurrence Handle10.1016/0039-128X(96)00044-X Occurrence Handle8776801 Occurrence Handle1:CAS:528:DyaK28XjsVKhtr0%3D

    Article  PubMed  CAS  Google Scholar 

  • T Miyazawa T Suzuki K Fujimoto (1993) ArticleTitleAge-dependent accumulation of phosphatidylcholine hydroperoxide in the brain and liver of the rat Lipids 28 789–793 Occurrence Handle8231654 Occurrence Handle1:CAS:528:DyaK3sXmsVKmsbo%3D

    PubMed  CAS  Google Scholar 

  • K Moorthy UC Yadav MR Siddiqui D Sharma SF Basir NZ Baquer (2004) ArticleTitleEffect of estradiol and progesterone treatment on carbohydrate metabolizing enzymes in tissues of aging female rats Biogerontology 5 249–259 Occurrence Handle15314275 Occurrence Handle1:CAS:528:DC%2BD2cXms12ju70%3D

    PubMed  CAS  Google Scholar 

  • K Moorthy D Sharma SF Basir NZ Baquer (2005) ArticleTitleAdministration of estradiol and progesterone modulate the activities of antioxidant enzyme and aminotransferases in naturally menopausal rats Exp Gerontol 40 295–302 Occurrence Handle10.1016/j.exger.2005.01.004 Occurrence Handle15820610 Occurrence Handle1:CAS:528:DC%2BD2MXjtlSru7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • VK Moudgil MS Kanungo (1973) ArticleTitleEffect of age of the rat on induction of acetylcholinesterase of the brain by 17 beta-estradiol Biochim Biophys Acta 329 211–220 Occurrence Handle4203345 Occurrence Handle1:CAS:528:DyaE2cXnvVKmsQ%3D%3D

    PubMed  CAS  Google Scholar 

  • M Mukherjee F Lorenzo ParticleDe Z Kadziola A Rutlin N Ranlall K Sembhi G Dawson VV Kakkar F DeLorenzo (1999) ArticleTitleCorrelation of circulating 17beta-oestradiol with haemostatic factors in healthy postmenopausal women Haemostasis 29 336–342 Occurrence Handle10.1159/000022521 Occurrence Handle10844407 Occurrence Handle1:CAS:528:DC%2BD3cXltFWntbs%3D

    Article  PubMed  CAS  Google Scholar 

  • MR Murthy (1966) ArticleTitleProtein synthesis in growing-rat tissues. Polyribosome concentration of brain and liver as a function of age Biochim Biophys Acta 119 599–613 Occurrence Handle5963029 Occurrence Handle1:CAS:528:DyaF28Xkt1egtLg%3D

    PubMed  CAS  Google Scholar 

  • H Namba M Iyo K Fukushi H Shinotoh S Nagatsuka T Suhara Y Sudo K Suzuki T Irie (1999) ArticleTitleHuman cerebral acetylcholinesterase activity measured with positron emission tomography: procedure, normal values and effect of age Euro J Nuc Med 26 135–143 Occurrence Handle1:CAS:528:DyaK1MXntFOgtw%3D%3D

    CAS  Google Scholar 

  • Y Noda PL McGeer EG McGeer (1982) ArticleTitleLipid peroxides in brain during aging and vitamin E deficiency: possible relations to changes in neurotransmitter indices Neurobiol Aging 3 173–178 Occurrence Handle10.1016/0197-4580(82)90037-9 Occurrence Handle6131387 Occurrence Handle1:CAS:528:DyaL3sXntVOguw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • CM Nomoto (2003) ArticleTitleClinical pharmacology and neuroprotection in Parkinson’s disease Parkinsonism Relat Disord 9 55–58 Occurrence Handle10.1016/S1353-8020(03)00044-0

    Article  Google Scholar 

  • A Oliverio BE Eleftheriou DW Bailey (1973) ArticleTitleExploratory activity: genetic analysis of its modification by scopolamine and amphetamine Physiol Behav 10 893–899 Occurrence Handle10.1016/0031-9384(73)90059-0 Occurrence Handle4715816 Occurrence Handle1:CAS:528:DyaE3sXltFWlsbg%3D

    Article  PubMed  CAS  Google Scholar 

  • JO Owasoya O Adeyemo CA Iramain (1980) ArticleTitleAcetylcholinesterase activity in seven brain areas and adenohypophysis during the estrous cycle Neurosci Lett 19 289–292

    Google Scholar 

  • A Pintor S Fortuna S De-Angelis H Michalek (1990) ArticleTitleImpaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl flurophosphate in aged rats Life Sci 46 1027–1036 Occurrence Handle10.1016/0024-3205(90)90027-O Occurrence Handle2325503 Occurrence Handle1:CAS:528:DyaK3cXhvFWrsrg%3D

    Article  PubMed  CAS  Google Scholar 

  • BV Ramasastry VE Janson N Jaiswal OS Tayeb (1983) ArticleTitleChanges in enzymes of the cholinergic system and acetylcholine release in the cerebra of aging male Fischer rats Pharmacology 26 61–72

    Google Scholar 

  • MMA Rodriguez T Ruiz (1992) ArticleTitleHomeostasis between lipid peroxidation and antioxidant enzymes activities in health human aging Mech Aging Dev 66 213–222

    Google Scholar 

  • D Roy DN Pathak R Singh (1983) ArticleTitleEffect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain Exp Gerontol 18 185–197 Occurrence Handle10.1016/0531-5565(83)90031-1 Occurrence Handle6416880 Occurrence Handle1:CAS:528:DyaL3sXmtVKjs7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • M Sawada JC Carlson (1987) ArticleTitleChanges in superoxide radical and lipid peroxide formation in the brain, heart and liver during the lifetime of the rat Mech Aging Dev 41 125–137 Occurrence Handle10.1016/0047-6374(87)90057-1 Occurrence Handle2828774 Occurrence Handle1:CAS:528:DyaL1cXnt1Oltw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • D Sharma R Singh (1994) ArticleTitleAge-Related changes in the number of lipofuscin containing neurons and neuronal histochemistry of lipofuscin and the effect of aging reversal drug centrophenoxine on senile neurons in the parietal cortex of rat PNAS Ind 60 523–534 Occurrence Handle1:CAS:528:DyaK2MXmsVKgtLo%3D

    CAS  Google Scholar 

  • D Sharma R Singh (1996) ArticleTitleAge-related decline in multiple unit action potentials of cerebral cortex correlates with the number of lipofuscin-containing neurons Ind J Exp Biol 34 776–781 Occurrence Handle1:STN:280:ByiC3svhtVA%3D

    CAS  Google Scholar 

  • MF Siddiqui AI Levey (1999) ArticleTitleCholinergic therapies in Alzheimer’s disease Drugs Fut 24 417–444 Occurrence Handle10.1358/dof.1999.024.04.668318 Occurrence Handle1:CAS:528:DyaK1MXktVeisbs%3D

    Article  CAS  Google Scholar 

  • S Takeda T Matsuzawa (1985) ArticleTitleAge-related brain atrophy: a study with computed tomography J Gerentol 40 159–163 Occurrence Handle1:STN:280:BiqC3s3ksVI%3D

    CAS  Google Scholar 

  • BP Yu (1996) ArticleTitleAging and oxidative stress: modulation by dietary restriction Free Radic Biol Med 21 651–668 Occurrence Handle10.1016/0891-5849(96)00162-1 Occurrence Handle8891668 Occurrence Handle1:CAS:528:DyaK28Xmt12ltr4%3D

    Article  PubMed  CAS  Google Scholar 

  • H Zhan CP Sun CG Liu JH Zhou (1992) ArticleTitleAge-related change of free radical generation in liver and sex glands of rats Mech Aging Dev 62 111–116 Occurrence Handle10.1016/0047-6374(92)90047-H Occurrence Handle1314923 Occurrence Handle1:CAS:528:DyaK38XhslSqtrs%3D

    Article  PubMed  CAS  Google Scholar 

  • I Zs.-Nagy (1985) ArticleTitleAgeing of the cellular membrane: basic principles and pharmacological interventions Geriatrika 1 102–111

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Najma Z. Baquer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moorthy, K., Yadav, U.C.S., Siddiqui, M.R. et al. Effect of Hormone Replacement Therapy in Normalizing Age Related Neuronal Markers in Different Age Groups of Naturally Menopausal Rats. Biogerontology 6, 345–356 (2005). https://doi.org/10.1007/s10522-005-4810-6

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-005-4810-6

Keywords

Navigation