Skip to main content
SpringerLink
Log in

MT2 Melatonin Receptor Immunoreactivity in Neurons is Very High in the Aged Hippocampal Formation in Gerbils

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Melatonin exerts many physiological functions via its G protein-coupled receptors. In the present study, we investigated age-related changes in MT2 melatonin receptor immunoreactivity and its levels in the gerbil hippocampus during normal aging. In the postnatal month 1 (PM 1) group, MT2 immunoreaction was well observed in neurons in all subregions of the gerbil hippocampus. In the PM 3 and 6 groups, MT2 immunoreactivity in neurons was decreased compared to that in the PM 1 group. Thereafter, MT2 immunoreactivity in neurons was increased. In the PM 18 and 24 groups, MT2 immunoreactivity in neurons was strong in all subregions of the gerbil hippocampus. In addition, the number of MT2 immunoreactive cells was lowest at PM 3 and highest at PM 24. From western blot analysis, age-dependent change pattern in MT2 level in the gerbil hippocampus was similar to the immunohistochemical result. These results indicate that MT2 immunoreactivity and levels are altered in the gerbil hippocampus during normal aging; lowest at young adult stage and highest at aged stage.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90:7915–7922

    Article  CAS  PubMed  Google Scholar 

  • Arendt J (1998) Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology. Rev Reprod 3:13–22

    Article  CAS  PubMed  Google Scholar 

  • Bustamante J, Czerniczyniec A, Cymeryng C, Lores-Arzaiz S (2008) Age related changes from youth to adulthood in rat brain cortex: nitric oxide synthase and mitochondrial respiratory function. Neurochem Res 33:1216–1223

    Article  CAS  PubMed  Google Scholar 

  • Carampin P, Rosan S, Dalzoppo D, Zagotto G, Zatta P (2003) Some biochemical properties of melatonin and the characterization of a relevant metabolite arising from its interaction with H2O2. J Pineal Res 34:134–142

    Article  CAS  PubMed  Google Scholar 

  • Dori D, Casale G, Solerte SB, Fioravanti M, Migliorati G, Cuzzoni G, Ferrari E (1994) Chrono-neuroendocrinological aspects of physiological aging and senile dementia. Chronobiologia 21:121–126

    CAS  PubMed  Google Scholar 

  • Dubocovich ML (1995) Melatonin receptors: are there multiple subtypes? Trends Pharmacol Sci 16:50–56

    Article  CAS  PubMed  Google Scholar 

  • Dubocovich ML, Markowska M (2005) Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27:101–110

    Article  CAS  PubMed  Google Scholar 

  • Dubocovich ML, Masana MI, Benloucif S (1999) Molecular pharmacology and function of melatonin receptor subtypes. Adv Exp Med Biol 460:181–190

    Article  CAS  PubMed  Google Scholar 

  • Ferrari E, Magri F, Dori D, Migliorati G, Nescis T, Molla G, Fioravanti M, Solerte SB (1995) Neuroendocrine correlates of the aging brain in humans. Neuroendocrinology 61:464–470

    Article  CAS  PubMed  Google Scholar 

  • Ferrari E, Arcaini A, Gornati R, Pelanconi L, Cravello L, Fioravanti M, Solerte SB, Magri F (2000) Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia. Exp Gerontol 35:1239–1250

    Article  CAS  PubMed  Google Scholar 

  • Gerdin MJ, Masana MI, Rivera-Bermúdez MA, Hudson RL, Earnest DJ, Gillette MU, Dubocovich ML (2004) Melatonin desensitizes endogenous MT2 melatonin receptors in the rat suprachiasmatic nucleus: relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin. FASEB J 18:1646–1656

    Article  CAS  PubMed  Google Scholar 

  • Hogan MV, El-Sherif Y, Wieraszko A (2001) The modulation of neuronal activity by melatonin: in vitro studies on mouse hippocampal slices. J Pineal Res 30:87–96

    Article  CAS  PubMed  Google Scholar 

  • Jack CR Jr, Petersen RC, Xu Y, O’Brien PC, Smith GE, Ivnik RJ, Boeve BF, Tangalos EG, Kokmen E (2000) Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 55:484–489

    PubMed  Google Scholar 

  • Karasek M (2004) Melatonin, human aging, and age-related diseases. Exp Gerontol 39:1723–1729

    Article  CAS  PubMed  Google Scholar 

  • King TS, Richardson BA, Reiter RJ (1981) Age-associated changes in pineal serotonin N-acetyltransferase activity and melatonin content in the male gerbil. Endocr Res Commun 8:253–262

    Article  CAS  PubMed  Google Scholar 

  • Knuttinen MG, Gamelli AE, Weiss C, Power JM, Disterhoft JF (2001) Age-related effects on eyeblink conditioning in the F344 × BN F1 hybrid rat. Neurobiol Aging 22:1–8

    Article  CAS  PubMed  Google Scholar 

  • Kotler M, Rodriguez C, Sáinz RM, Antolín I, Menéndez-Peláez A (1998) Melatonin increases gene expression for antioxidant enzymes in rat brain cortex. J Pineal Res 24:83–89

    Article  CAS  PubMed  Google Scholar 

  • LeBel CP, Bondy SC (1992) Oxidative damage and cerebral aging. Prog Neurobiol 38:601–609

    Article  CAS  PubMed  Google Scholar 

  • Leger D, Laudon M, Zisapel N (2004) Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am J Med 116:91–95

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Atamna H, Kuratsune H, Ames BN (2002) Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann N Y Acad Sci 959:133–166

    Article  CAS  PubMed  Google Scholar 

  • Loskota WA, Lomax P, Verity MA (1974) A stereotaxic atlas of the Mongolian Gerbil brain (Meriones unguiculatus). Ann Arbor Science Publishers Inc, Michigan, pp 70–79

    Google Scholar 

  • Magri F, Locatelli M, Balza G, Molla G, Cuzzoni G, Fioravanti M, Solerte SB, Ferrari E (1997) Changes in endocrine circadian rhythms as markers of physiological and pathological brain aging. Chronobiol Int 14:385–396

    Article  CAS  PubMed  Google Scholar 

  • Musshoff U, Riewenherm D, Berger E, Fauteck JD, Speckmann EJ (2002) Melatonin receptors in rat hippocampus: molecular and functional investigations. Hippocampus 12:165–173

    Article  CAS  PubMed  Google Scholar 

  • Payão SL, de Carvalho CV, da Silva ER, Lopes C, Markus RP, Winter LM, Smith MA (2001) Pinealectomy-associated decrease in ribosomal gene activity in rats. Biogerontology 2:105–108

    Article  PubMed  Google Scholar 

  • Petersen RC, Jack CR Jr, Xu YC, Waring SC, O’Brien PC, Smith GE, Ivnik RJ, Tangalos EG, Boeve BF, Kokmen E (2000) Memory and MRI-based hippocampal volumes in aging and AD. Neurology 54:581–587

    CAS  PubMed  Google Scholar 

  • Pierpaoli W (1998) Neuroimmunomodulation of aging. A program in the pineal gland. Ann N Y Acad Sci 840:491–497

    Article  CAS  PubMed  Google Scholar 

  • Reiter RJ, Richardson BA, Johnson LY, Ferguson BN, Dinh DT (1980) Pineal melatonin rhythm: reduction in aging Syrian hamsters. Science 210:1372–1373

    Article  CAS  PubMed  Google Scholar 

  • Reiter RJ, Tan D, Kim SJ, Manchester LC, Qi W, Garcia JJ, Cabrera JC, El-Sokkary G, Rouvier-Garay V (1999) Augmentation of indices of oxidative damage in life-long melatonin-deficient rats. Mech Ageing Dev 110:157–173

    Article  CAS  PubMed  Google Scholar 

  • Reiter RJ, Tan DX, Osuna C, Gitto E (2000) Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci 7:444–458

    Article  CAS  PubMed  Google Scholar 

  • Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (1995) Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci USA 92:8734–8738

    Article  CAS  PubMed  Google Scholar 

  • Sánchez-Hidalgo M, Guerrero Montávez JM, Carrascosa-Salmoral Mdel P, Naranjo Gutierrez Mdel C, Lardone PJ, a Romero CA (2009) Decreased MT1 and MT2 melatonin receptor expression in extrapineal tissues of the rat during physiological aging. J Pineal Res 46:29–35

    Article  PubMed  CAS  Google Scholar 

  • Savaskan E, Ayoub MA, Ravid R, Angeloni D, Fraschini F, Meier F, Eckert A, Müller-Spahn F, Jockers R (2005) Reduced hippocampal MT2 melatonin receptor expression in Alzheimer’s disease. J Pineal Res 38:10–16

    Article  CAS  PubMed  Google Scholar 

  • Schmerold I, Niedermüller H (2001) Levels of 8-hydroxy-2′-deoxyguanosine in cellular DNA from 12 tissues of young and old Sprague-Dawley rats. Exp Gerontol 36:1375–1386

    Article  CAS  PubMed  Google Scholar 

  • Squire LR (1992) Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev 99:195–231

    Article  CAS  PubMed  Google Scholar 

  • Touitou Y (2001) Human aging and melatonin. Clinical relevance. Exp Gerontol 36:1083–1100

    Article  CAS  PubMed  Google Scholar 

  • Touitou Y, Reinberg A, Bogdan A, Auzéby A, Beck H, Touitou C (1986) Age-related changes in both circadian and seasonal rhythms of rectal temperature with special reference to senile dementia of Alzheimer type. Gerontology 32:110–118

    Article  CAS  PubMed  Google Scholar 

  • Troen BR (2003) The biology of aging. Mt Sinai J Med 70:3–22

    PubMed  Google Scholar 

  • Wan Q, Man HY, Liu F, Braunton J, Niznik HB, Pang SF, Brown GM, Wang YT (1999) Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors. Nat Neurosci 2:401–403

    Article  CAS  PubMed  Google Scholar 

  • Wei YH, Lee HC (2002) Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med 227:671–682 (Maywood)

    CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Mr. Seung Uk Lee and Ms. Hyun Sook Kim for their technical help in this study. This research was a part of the project titled “Development of functional ingredients and product from marine resources for improving cognitive ability” funded by the Ministry of Land, Transport and Maritime Affairs, Korea.

Author information

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, and Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea

    Choong Hyun Lee, Jung Hoon Choi, Ki-Yeon Yoo, Ok Kyu Park & Moo-Ho Won

  2. Department of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    In Koo Hwang

  3. Marine Food Science and Technology, Kangnung-Wonju National University, Gangneung, 210-702, South Korea

    Sang Guan You

  4. Department of Biomedical Science, CHA University, Seongnam, 463-836, South Korea

    Boo-Yong Lee

  5. Department of Food Science and Nutrition, Hallym University, Chuncheon, 200-702, South Korea

    Il-Jun Kang

Authors
  1. Choong Hyun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jung Hoon Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ki-Yeon Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ok Kyu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. In Koo Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sang Guan You
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Boo-Yong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Il-Jun Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Moo-Ho Won
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moo-Ho Won.

Additional information

Choong Hyun Lee and Jung Hoon Choi contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, C.H., Choi, J.H., Yoo, KY. et al. MT2 Melatonin Receptor Immunoreactivity in Neurons is Very High in the Aged Hippocampal Formation in Gerbils. Cell Mol Neurobiol 30, 255–263 (2010). https://doi.org/10.1007/s10571-009-9447-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-009-9447-6

Keywords

Search

Navigation