Melatonin and the aging brain

Bondy, Stephen C.; Sharman, Edward

doi:10.1016/j.neuint.2006.12.014

Cited by 44 publications

(30 citation statements)

References 127 publications

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“…In addition, the nighttime synthesis/release of MLT is significantly blunted in old as compared to adult and young rats. These data are congruent with the decline in pineal MLT production in the old rats as compared to adult and young rats reported in other rodents [22,23] and in humans [24,25]. As we and others have demonstrated the oncostatic effects of MLT on human breast cancer [10,11] and rat mammary tumors [7][8][9], we predict that in response to the diminution of MLT serum levels with the onset of old age, mammary and breast tumor growth will be accelerated even in the presence of diminished ovarian17-b estradiol.…”

Section: Discussionsupporting

confidence: 91%

RETRACTED ARTICLE: Declining melatonin levels and MT1 receptor expression in aging rats is associated with enhanced mammary tumor growth and decreased sensitivity to melatonin

Hill

Cheng

Yuan

et al. 2010

Breast Cancer Res Treat

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Serum melatonin (MLT) levels have been reported to diminish significantly by the 5th and 6th decades of life as the incidence of breast cancer increases. Given MLT's anti-cancer activity, we hypothesize that age-related decline in pineal MLT production leads to enhanced breast cancer development and growth as women age. In this study, we sought to determine whether the growth of tissue-isolated mammary tumors in young, adult, and old female Buffalo rats relates to the age-related changes in MLT and its MT1 receptor. Significant decreases in the peak nighttime serum MLT levels were observed in old as compared to adult and young rats. Significantly diminished nighttime and early morning levels of MT1-melatonin receptors were observed in uteri from old rats compared to adult and young rats. Growth rates in transplanted, tissue-isolated, carcinogen-induced mammary tumors are significantly increased in old rats as compared to adult or young rats. The growth-suppressive actions of exogenous MLT are diminished in old rats compared to adult and young rats. This decrease in tumor response correlates with reduced expression of the MT1 receptor in old as compared to young and adult rats. Thus, enhanced mammary tumor growth is associated with old age and diminished levels of MLT and MT1 receptor during old age, resulting in reduced sensitivity to exogenous MLT. Finally, our studies demonstrate that the tissue-isolated tumor model is viable model system in which to study the role of aging on breast cancer growth.

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Section: Discussionsupporting

confidence: 91%

RETRACTED ARTICLE: Declining melatonin levels and MT1 receptor expression in aging rats is associated with enhanced mammary tumor growth and decreased sensitivity to melatonin

Hill

Cheng

Yuan

et al. 2010

Breast Cancer Res Treat

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“…Other effects of melatonin are inhibition of dopamine release in hypothalamus and retina [1]. The anti-excitatory effects of melatonin are probably secondary to its antioxidant effect [5]. When it is administered in pharmacological doses in children, it leads to reduction in severity and frequency of epileptiform activity [6].…”

Section: öZmentioning

confidence: 99%

A Review of Melatonin, Its Receptors and Drugs

et al. 2016

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After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activityregulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future. Keywords: Melatonin, receptors, agonists, pineal gland ÖzSaat genlerini anlamamıza olan katkısından dolayı bir Türk bilim adamı Nobel ödülünü aldıktan sonra, bu genlerle yakın ilişkili olan melatoninin önemi arttı. Melatonin, pineal bezden gece salınan bir hormondur, uyku/uyanıklık döngüsünde, pubertal gelişimde ve mevsimsel adaptasyonda rol alır. Melatoninin antinosiseptif, antidepresan, anksiyolitik, antineofobik, locomotor aktiviteyi düzenleyici, nöroprotektif, antiinflamatuvar, ağrı dü-zenleyici, kan basıncını düşürücü, retinal, vasküler, tümör baskılayıcı ve antioksidan etkileri vardır. Hafıza, over fizyolojisi ve osteoblast diferansiasyonuyla ilişkilidir. Melatonin seviyelerinde artış veya azalışla seyreden patolojiler derlemede özetlenmiştir. Melatonin 4 mekanizmayla etkir: 1) Plazma membranında melatonin reseptörlerine bağlanma, 2) Kalmodulin gibi hücre içi reseptörlere bağlanma, 3) Yetim nükleer reseptörlere bağlanma, 4) Antioksidan etkiler. Melatoninle ilişkili reseptörler şunlardır: 1) Melatonin reseptör tip1a: MT1 (hücre zarında), 2) Melatonin reseptör tip1b: MT2 (hücre zarında), 3) Melatonin reseptör tip1c (balık, amfibiler ve kuşlarda bulunur), 4) Kuinon redüktaz-2 enzimi (MT3 reseptörü, bir detoksifika...

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“…Changes in these signaling pathways may form the basis of the alteration in gene expression effected by melatonin. The linkage between reduced melatonin levels and accelerated aging has been reviewed elsewhere (Bondy & Sharman, 2007) and may be more than merely correlative. Levels of both MT 1 and MT 2 receptors are very high within the suprachiasmatic nucleus (SCN), the site of circadian rhythm regulation.…”

Section: Melatonin Receptorsmentioning

confidence: 99%