Skip to main content

Advertisement

Log in

Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions

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

An Erratum to this article was published on 03 June 2008

Abstract

Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer and others. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. Thus, DHEA is considered to be a neuroactive pharmacological substance with potential antiaging properties. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO). Increased MAO activity with correlated increase in lipid peroxidation in the aging rat brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress. The progressive accumulation of lipofuscin in neuronal cells is one of the most characteristic age related changes, an increase in body weight was also observed at 24 months. The objective of this study was to observe the changes in monoamine oxidase activity, lipid peroxidation levels and lipofuscin accumulation occurring in aging rat brain regions, and to see whether these changes are restored to normal levels after exogenous administration of DHEA (30 mg/kg/day for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in brain regions of 4, 14 and 24 months age group male rats. The present study showed that DHEA treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, the increased body weight at 24 months also decreased more than the age matched controls. It can therefore be suggested that DHEA’s beneficial effects seemed to arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. The results of this study will be useful for pharmacological modification of the aging process and development of new drugs for age related 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.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

CNS:

Central nervous system

DHEA:

Dehydroepiandrosterone

DHEAS:

Dehydroepiandrosterone-sulphate

DMSO:

Dimethylsulphoxide

GABA:

Gamma-aminobutyric acid

MAO:

Monoamine oxidase

MDA:

Malondialdehyde

NMDA:

N-methyl-d-aspartate

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

TBARS:

Thiobarbituric acid reactive substance

References

  • Abrass IB (1990) The biology and physiology of aging. West J Med 153:641–645

    PubMed  CAS  Google Scholar 

  • Alper G, Girgin FK, Ozgonul M, Mentes G, Ersoz B (1999) MAO inhibitors and oxidant stress in aging brain tissue. Eur Neuropsychopharmacol 9:247–252

    Article  PubMed  CAS  Google Scholar 

  • Bala K, Tripathy BC, Sharma D (2006) Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions. Biogerontology 7:81–90

    Article  PubMed  CAS  Google Scholar 

  • Baulieu EE, Robel P (1996) Dehydroepiandrosterone and dehydroepiandrosterone sulfate as neuroactive neurosteroids. J Endocrinol 150:221–239

    Google Scholar 

  • Benedetti MS, Dostert P (1989) Monoamine oxidase, brain ageing and degenerative diseases. Biochem Pharmacol 38:555–561

    Article  Google Scholar 

  • Berdanier CD, Parente JA Jr, McIntosh MK (1993) Is dehydroepiandrosterone an antiobesity agent? FASEB 7:414–419

    CAS  Google Scholar 

  • Bergeron R, de Montigny C, Debonnel G (1996) Potentiation of neuronal NMDA response induced by dehydroepiandrosterone and its suppression by progesterone: effects mediated via sigma receptors. J Neurosci 16:1193–1202

    PubMed  CAS  Google Scholar 

  • Boccuzzi G, Aragno M, Seccia M, Brignardello E, Tamagno E, Albano E, Danni O, Bellomo G (1997) Protective effect of dehydroepiandrosterone against copper-induced lipid peroxidation in the rat. Free Radic Biol Med 22:1289–1294

    Article  PubMed  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Cardounel A, Regelson W, Kalimi M (1999) Dehydroepiandrosterone protects hippocampal neurons against neurotoxin-induced cell death: mechanism of action. Proc Soc Exp Biol Med 222:145–149

    Article  PubMed  CAS  Google Scholar 

  • Cardozo-Pelaez F, Brooks PJ, Stedeford T, Song S, Sanchez-Ramos J (2000) DNA damage, repair, and antioxidant systems in brain regions: a correlative study. Free Radic Biol Med 28:779–785

    Article  PubMed  CAS  Google Scholar 

  • Catravas GN, Takenaga J, McHale CG (1977) Effect of chronic administration of morphine on monoamine oxidase activity in discrete regions of the brain of rats. Biochem Pharmacol 26:211–214

    Article  PubMed  CAS  Google Scholar 

  • Celec P, Starka L (2003) Dehydroepiandrostreone – is the fountain of youth drying out? Physiol Res 52:397–407

    PubMed  CAS  Google Scholar 

  • Cleary MP (1991) The antiobesity effect of dehydroepiandrosterone in rats. Proc Soc Exp Biol Med 196:8–16

    PubMed  CAS  Google Scholar 

  • Compagnone NA, Mellon SH (2000) Neurosteroids: biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol 21:1–56

    Article  PubMed  CAS  Google Scholar 

  • Drach LM, Bohl J, Goebel HH (1994) The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer’s disease. Dementia 5:234–239

    Article  PubMed  CAS  Google Scholar 

  • Flood JF, Smith GE, Roberts E (1988) Dehydroepiandrosterone and its sulfate enhance memory retention in mice. Brain Res 447:269–278

    Article  PubMed  CAS  Google Scholar 

  • Fosslien E (2001) Mitochondrial medicine–molecular pathology of defective oxidative phosphorylation. Ann Clin Lab Sci 31:25–67

    PubMed  CAS  Google Scholar 

  • Fowler CJ, Tipton KF (1984) On the substrate specificities of the two forms of monoamine oxidase. J Pharm Pharmacol 36:111–115

    PubMed  CAS  Google Scholar 

  • Garcia de Yebenes E, Hong M, Pelletier G (1995) Effects of dehydroepiandrosterone (DHEA) on pituitary prolactin and arcuate nucleus neuron tyrosine hydroxylase mRNA levels in the rat. J Neuroendocrinol 7:589–595

    Article  Google Scholar 

  • Genet S, Kale RK, Baquer NZ (2002) Alterations in antioxidant enzymes and oxidative damage in experimental diabetic rat tissues: effect of vanadate and fenugreek (Trigonella foenum graecum). Mol Cell Biochem 236:7–12

    Article  PubMed  CAS  Google Scholar 

  • Hagihara M, Nishigaki I, Maseki M, Yagi K (1984) Age-dependent changes in lipid peroxide levels in the lipoprotein fractions of human serum. J Gerontol 39:269–272

    PubMed  CAS  Google Scholar 

  • Harman D (1993) Free radical involvment in aging: pathophysiology and therapeutic implications. Drugs Aging 3: 60–80

    Article  PubMed  CAS  Google Scholar 

  • Hauptmann N, Grimsby J, Shih JC, Cadenas E (1996) The metabolism of tyramine by monoamine oxidase A/B causes oxidative damage to mitochondrial DNA. Arch Biochem Biophys 335: 295–304

    Article  PubMed  CAS  Google Scholar 

  • Jahng JW, Houpt TA, Wessel TC, Chen K, Shih JC, Joh TH (1997) Localization of monoamine oxidase A and B mRNA in the rat brain by in situ hybridization. Synapse 25:30–36

    Article  PubMed  CAS  Google Scholar 

  • Kaur J, Sharma D, Singh R (2001) Acetyl-L-carnitine enhances Na (+), K(+)-ATPase glutathione-S-transferase and multiple unit activity and reduces lipid peroxidation and lipofuscin concentration in aged rat brain regions. Neurosci Lett 301:1–4

    Article  PubMed  CAS  Google Scholar 

  • Kaur J, Singh S, Sharma D, Singh R (2003) Neurostimulatory and antioxidative effects of l-deprenyl in aged rat brain regions. Biogerontology 4:105–111

    Article  PubMed  CAS  Google Scholar 

  • Kazihnitková H, Tejkalová H, Benesová O, Bicíková M, Hill M, Hampl R (2004) Simultaneous determination of dehydroepiandrosterone, its 7-hydroxylated metabolites, and their sulfates in rat brain tissues. Steroids 69:667–674

    Article  PubMed  CAS  Google Scholar 

  • Khorram O, Vu L, Yen SS (1997) Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men. J Gerontol A Biol Sci Med Sci 52:1–7

    Google Scholar 

  • Kimonides VG, Khatibi NH, Svendsen CN, Sofroniew MV, Herbert J (1998) Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. Proc Natl Acad Sci USA 95:1852–1857

    Article  PubMed  CAS  Google Scholar 

  • Knoll J (1993) The pharmacological basis of the beneficial effects of (−) deprenyl (selegiline) in Parkinson’s and Alzheimer’s diseases. J Neural Transm Suppl 40:69–91

    PubMed  CAS  Google Scholar 

  • Labrie F, Diamond P, Cusan L, Gomez JL, Candas B (1997) Effect of 12 month dehdroepiendrosterone replacement therapy on bone, vagina and endometricum in post-menopausal women. J clin Endrocrinol metab 82:3498–3505

    Article  CAS  Google Scholar 

  • Lhullier FL, Riera NG, Nicolaidis R, Junqueira D, Dahm KC, Cipriani F, Brusque AM, Souza DO (2004) Effect of DHEA glutamate release from synaptosomes of rats at different ages. Neurochem Res 29:335–339

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Wang X, Shigenaga MK, Yeo HC, Mori A, Ames BN (1996) Immobilization stress causes oxidative damage to lipid, protein and DNA in the brain of rats. FASEB J 10:1532–1538

    PubMed  CAS  Google Scholar 

  • Lucas JA, Ahmed SA, Casey LM, Mc Donald PC (1985) Prevention autoantibody formation and prolonged survival in New-Zealand Black/New Zealand White F1 mice fed dehydroepiandrosterone. J Clin Invest 75:2091–2093

    Article  PubMed  CAS  Google Scholar 

  • Marklund SL, Westman NG, Lundgren E, Roos G (1982) Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res 42:1955–1961

    PubMed  CAS  Google Scholar 

  • Marx CE, Jarskog LF, Lauder JM, Gilmore JH, Lieberman JA, Morrow AL (2000) Neurosteroid modulation of embryonic neuronal survival in vitro following anoxia. Brain Res 871:104–112

    Article  PubMed  CAS  Google Scholar 

  • Mayanil CS, Kazmi SM, Baquer NZ (1982) Changes in monoamine oxidase activity in rat brain during alloxan diabetes. J Neurochem 38:179–183

    Article  PubMed  CAS  Google Scholar 

  • Miyazawa T, Suzuki T, Fujimoto K (1993) Age-dependent accumulation of phosphatidylcholine hydroperoxide in the brain and liver of the rat. Lipids 28:789–793

    Article  PubMed  CAS  Google Scholar 

  • Moorthy K, Yadav UC, Siddiqui MR, Mantha AK, Basir SF, Sharma D, Cowsik SM, Baquer NZ (2005) Effect of hormone replacement therapy in normalizing age related neuronal markers in different age groups of naturally menopausal rats. Biogerontology 6:345–356

    Article  PubMed  CAS  Google Scholar 

  • Noda Y, McGeer PL, McGeer EG (1982) Lipid peroxides in brain during aging and vitamin E deficiency: possible relations to changes in neurotransmitter indices. Neurobiol Aging 3:173–178

    Article  PubMed  CAS  Google Scholar 

  • Oreland L, Gottfries CG (1986) Brain and brain monoamine oxidase in aging and in dementia of Alzheimer’s type. Prog Neuropsychopharmacol Biol Psychiatry 10:533–540

    Article  PubMed  CAS  Google Scholar 

  • Orentreich N, Brind JL, Rizer RL, Vogelman JH (1984) Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metabol 59:551–555

    Article  CAS  Google Scholar 

  • Racchi M, Balduzzi C, Corsini E (2003) Dehdroepiendrosterone (DHEA) and the aging brain: flipping a coin in the ‘‘fountain of youth’’. CNS Drug Rev 9:21–40

    Article  PubMed  CAS  Google Scholar 

  • Reiter EO, Fuldauer VG, Root AW (1977) Secretion of the adrenal androgen, dehydroepiandrosterone sulfate, during normal infancy, childhood, and adolescence, in sick infants, and in children with endocrinologic abnormalities. J Pediatr 90:766–770

    Article  PubMed  CAS  Google Scholar 

  • Riga S, Riga D (1974) Effects of centrophenoxine on the lipofuscin pigments in the nervous system of old rats. Brain Res 72:265–275

    Article  PubMed  CAS  Google Scholar 

  • Richardson JS, Subbarao KV, Ang LC (1992) On the possible role of iron-induced free radical peroxidation in neural degeneration in Alzheimer’s disease. Ann NY Acad Sci 648:326–327

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez MMA, Ruiz TA (1992) Homeostasis between lipid peroxidation and antioxidant enzymes activities in health human aging. Mech Ageing Dev 66:213–222

    Article  Google Scholar 

  • Saura J, Richards JG, Mahy N (1994) Differential age-related changes of MAO-A and MAO-B in mouse brain and peripheral organs. Neurobiol Aging 15:399–408

    Article  PubMed  CAS  Google Scholar 

  • Schuessel K, Frey C, Jourdan C, Keil U, Weber CC, Muller-Spahn F, Muller WE, Eckert A (2006) Aging sensitizes toward ROS formation and lipid peroxidation in PS1M146L transgenic mice. Free Radic Biol Med 40:850–862

    Article  PubMed  CAS  Google Scholar 

  • Sharma D, Maurya AK, Singh R (1993) Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine. Neurobiol Aging 14:319–330

    Article  PubMed  CAS  Google Scholar 

  • Sinet PM, Heikkila RE, Cohen G (1980) Hydrogen peroxide production by rat brain in vivo. J Neurochem 34:1421–1428

    Article  PubMed  CAS  Google Scholar 

  • Sinha N, Baquer NZ, Sharma D (2005) Anti-lipidperoxidative role of exogenous dehydroepiandrosterone (DHEA) administration in normal ageing rat brain. Indian J Exp Biol 43:420–424

    PubMed  CAS  Google Scholar 

  • Sinha N, Taha A, Baquer NZ, Sharma D (2008) Exogenous administration of Dehydroepiendrosterone attenuates loss of superoxide dismutase activity in the brain of old rats. Indian J Biochem Biophys 45:57–60

    CAS  Google Scholar 

  • Sohal RS, Brunk UT (1989) Lipofuscin as an indicator of oxidative stress and aging. Adv Exp Med Biol 266:17–26

    PubMed  CAS  Google Scholar 

  • Terman A, Brunk UT (2004) Aging as a catabolic malfunction. Int J Biochem Cell Biol 36:2365–2375

    Article  PubMed  CAS  Google Scholar 

  • Vedder H, Anthes N, Stumm G, Wurz C, Behl C, Krieg JC (1999) Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system. J Neurochem 72:2531–2538

    Article  PubMed  CAS  Google Scholar 

  • Weaver CE, Jr Marek P, Park-Chung M, Tam SW, Farb DH (1997) Neuroprotective activity of a new class of steroidal inhibitors of the N-methyl-d-aspartate receptor. Proc Natl Acad Sci USA 94:10450–10454

    Article  PubMed  CAS  Google Scholar 

  • Wen S, Dong K, Onolfo JP, Vincens M (2001) Treatment with Dehydroepiandrosterone sulfate increases NMDA receptors in hippocampus and cortex. Eur J Pharmacol 430:373–374

    Article  PubMed  CAS  Google Scholar 

  • Wolf OT, Kirschbaum C (1999) Actions of dehydroepiandrosterone and its sulfate in the central nervous system: effect on cognition and emotion in animals and human. Brain Res Rev 30:264–288

    Article  PubMed  CAS  Google Scholar 

  • Yen TT, Allen JA, Pearson DV, Action JM, Greemberg M M (1977) Prevention of obesity in Avy/a mice by dehydroepiandrosterone. Lipids 12:409–413

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors Pardeep Kumar, Dr. Asia Taha and Prof. N.Z. Baquer are grateful to the financial support from Council of Scientific and Industrial Research in the form of junior and senior research fellowships from Indian Council of Medical Research and emeritus fellowship from University Grants Commission, New Delhi, India respectively.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Najma Z. Baquer.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s10522-008-9148-4

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, P., Taha, A., Sharma, D. et al. Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions. Biogerontology 9, 235–246 (2008). https://doi.org/10.1007/s10522-008-9133-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-008-9133-y

Keywords

Navigation