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A Review of Pinealectomy-Induced Melatonin-Deficient Animal Models for the Study of Etiopathogenesis of Adolescent Idiopathic Scoliosis  [PDF]
Man Gene Chi Wai,Wang William Wei Jun,Yim Annie Po Yee,Wong Jack Ho,Ng Tzi Bun,Lam Tsz Ping,Lee Simon Kwong Man,Ng Bobby Kin Wah,Wang Chi Chiu,Qiu Yong,Cheng Jack Chun Yiu
International Journal of Molecular Sciences , 2014, DOI: 10.3390/ijms150916484
Abstract: Adolescent idiopathic scoliosis (AIS) is a common orthopedic disorder of unknown etiology and pathogenesis. Melatonin and melatonin pathway dysfunction has been widely suspected to play an important role in the pathogenesis. Many different types of animal models have been developed to induce experimental scoliosis mimicking the pathoanatomical features of idiopathic scoliosis in human. The scoliosis deformity was believed to be induced by pinealectomy and mediated through the resulting melatonin-deficiency. However, the lack of upright mechanical spinal loading and inherent rotational instability of the curvature render the similarity of these models to the human counterparts questionable. Different concerns have been raised challenging the scientific validity and limitations of each model. The objectives of this review follow the logical need to re-examine and compare the relevance and appropriateness of each of the animal models that have been used for studying the etiopathogenesis of adolescent idiopathic scoliosis in human in the past 15 to 20 years.
Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: similarity with polycystic ovary syndrome
Prata Lima, M.F.;Baracat, E.C.;Sim?es, M.J.;
Brazilian Journal of Medical and Biological Research , 2004, DOI: 10.1590/S0100-879X2004000700007
Abstract: the current study was conducted to investigate the relationship between melatonin and chronic anovulation. adult (3-4 months old) female wistar rats were submitted to pinealectomy: group i: pinealectomized ovariectomized melatonin-treated (n = 10); group ii: pinealectomized ovariectomized placebo-treated (n = 12); group iii: pinealectomized light-treated placebo-treated(n = 10) or maintained under continuous light; group iv: maintained under continuous light, ovariectomized melatonin-treated (n = 22); group v: maintained under continuous light, ovariectomized placebo-treated (n = 10); group vi: maintained under continuous light placebo-treated (n = 10). in order to assess ovarian modifications, unilateral ovariectomy was performed during the fourth month in groups i, ii, iv, v and the other ovary was removed after 8 months. ovariectomy was performed in groups iii and vi only after eight months. melatonin (200 μg/100 g body weight) dissolved in 0.02 ml absolute ethanol was injected intramuscularly daily during the last 4 months into groups i and iv. the other groups were treated with placebo (nacl). the ovarian cysts were analyzed and their area, perimeter and maximum diameter, as well as the thickness of the ovarian capsule were measured. daily colpocytological smears were performed throughout the study. persistent estrous condition and ovarian cysts were observed in all groups. in pinealectomized rats the ovarian and vaginal alterations disappeared at the end of the study and in rats maintained under continuous light the vaginal and ovarian polycystic aspect was reversed only in those treated with melatonin. we conclude that melatonin may act on the ovarian response reverting chronic anovulation induced by pinealectomy or continuous light.
Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: similarity with polycystic ovary syndrome  [cached]
Prata Lima M.F.,Baracat E.C.,Sim?es M.J.
Brazilian Journal of Medical and Biological Research , 2004,
Abstract: The current study was conducted to investigate the relationship between melatonin and chronic anovulation. Adult (3-4 months old) female Wistar rats were submitted to pinealectomy: group I: pinealectomized ovariectomized melatonin-treated (N = 10); group II: pinealectomized ovariectomized placebo-treated (N = 12); group III: pinealectomized light-treated placebo-treated(N = 10) or maintained under continuous light; group IV: maintained under continuous light, ovariectomized melatonin-treated (N = 22); group V: maintained under continuous light, ovariectomized placebo-treated (N = 10); group VI: maintained under continuous light placebo-treated (N = 10). In order to assess ovarian modifications, unilateral ovariectomy was performed during the fourth month in groups I, II, IV, V and the other ovary was removed after 8 months. Ovariectomy was performed in groups III and VI only after eight months. Melatonin (200 μg/100 g body weight) dissolved in 0.02 ml absolute ethanol was injected intramuscularly daily during the last 4 months into groups I and IV. The other groups were treated with placebo (NaCl). The ovarian cysts were analyzed and their area, perimeter and maximum diameter, as well as the thickness of the ovarian capsule were measured. Daily colpocytological smears were performed throughout the study. Persistent estrous condition and ovarian cysts were observed in all groups. In pinealectomized rats the ovarian and vaginal alterations disappeared at the end of the study and in rats maintained under continuous light the vaginal and ovarian polycystic aspect was reversed only in those treated with melatonin. We conclude that melatonin may act on the ovarian response reverting chronic anovulation induced by pinealectomy or continuous light.
The Effects of Pinealectomy and Melatonin Implants on Circadian Locomotor Activity Responses of the Mongolian Gerbils Exposed to Rapid Photoperiodic Transitions  [PDF]
Bülent GüNDüZ,Alper KARAKA?
Journal of Neurological Sciences , 2010,
Abstract: The jet-lag syndrome and the shift-work malaise take place by rapid changes in photoperiod and disturb people's life frequently. In the present study; we wanted to simulate these conditions. Control, pinealectomized and melatonin including silastic tube implanted Mongolian gerbils were respectively exposed into long (14L:10D), short (8L:16D), constant darkness (0L:24D) and constant light (24L:0D) photoperiods in order to investigate the effects of photoperiod, pineal gland and melatonin hormone in the photoperiodic reentrainment of this species. Gerbils showed an light/dark cycle entrained locomotor activity rhythm in long and short photoperiods, free-running in constant darkness and arrhythmic locomotor activity in constant light. The period lengths were similar to each other in the groups (p>0,05). Gerbils were reentrained by the changes in photoperiod nevertheless pinealectomy and melatonin implants did not make any significant influence on this reentrainment (p>0,05). Locomotor activity amounts varied in a group-photoperiod-dependent manner. These data suggest that photoperiod but not the pineal gland and constant release melatonin hormone is effective on the activity rhythm of the Mongolian gerbil.
Effects of Exogenous Melatonin on Body Mass Regulation and Hormone Concentrations in Eothenomys miletus  [PDF]
Zhu, Wan-Long,Zhang, Di,Zhang, Lin,Wang, Zheng-Kun
Journal of Stress Physiology & Biochemistry , 2013,
Abstract: By regulating the pineal hormone, photoperiods affect many physiological characteristics in small mammals. Thus, melatonin might take part in the thermoregulation of seasonal variations in small mammals. This study determined the influence of melatonin treatment on thermogenic pattern, we measured body mass, thermogenic activities and hormone concentrations of Eothenomys miletus were given exogenous melatonin (MLT) for 28 days. The results shown that body mass was reduced significantly, whereas resting metabolic rate (RMR) and nonshivering thermogenesis (NST) increased at 28 days in MLT group compared to control group as well as the oxidative capacities of mitochondria in liver and brown adipose tissue (BAT) were enhanced; the contents of total and mitochodrial protein increased markedly. Melatonin treatment significantly increased the State 3, State 4 respiration of liver mitochondria, and the activity of cytochrome C oxidase (COX) in liver; but the α-glerocephasphate oxidase (α-PGO) capacity showed no differences during the acclimation in liver. Furthermore, the State 4 respiration, the activities of COX and α-PGO in BAT increased, respectively. The activity of thyroxin 5’-deiodinase ( T45’-DII) in BAT increased remarkably. The serum content of thyroxine (T 4) decreased, and that of tri-iodothyronine (T 3) increased. Moreover, serum leptin levels showed no significant differences in MLT group compared to control group. Together, these data indicate that melatonin enhances thermogenic capacity in E. miletus. Our results suggested that melatonin is potentially involved in the regulation of body mass, adaptive thermogenic capacity and hormone concentrations in E. miletus.
The pineal neurohormone melatonin and its physiologic opiatergic immunoregulatory role
Maestroni, Georges J. M.;Conti, Ario;Pierpaoli, Walter;
Memórias do Instituto Oswaldo Cruz , 1987, DOI: 10.1590/S0074-02761987000600012
Abstract: the pineal gland functions as a neuroendocrine transducer that coordinate the organism response to changing environmental stimuli such as light and temperature. the main and best known pineal neurohormone is melatonin that is synthesized and released in a circadian fashion with a peak during the night darkness hours. we have recently reported that melatonin exerts important immuno regulatory functions. here we describe the astonishing property of exogenous melatonin which is able to counteract completely the depressive effect of anxiety-restraint stress and/or of corticosterone on thymus weight, andibody production and antiviral responses. this effect seems to be mediated by antigen-activated t cells via an opiatergic mechanism.
Possible Role of Exogenous Melatonin and Melatonin-Receptor-Agonists in the Treatment of Menopause―Associated Sleep Disturbances  [PDF]
Amnon Brzezinski
Open Journal of Obstetrics and Gynecology (OJOG) , 2014, DOI: 10.4236/ojog.2014.46047
Abstract:

One of the core symptoms of the menopausal transition is sleep disturbance. Peri-menopausal women often complain of difficulties initiating and/or maintaining sleep with frequent nocturnal and early morning awakenings. Factors that may play a role in this type of insomnia include vasomotor symptoms and changing reproductive hormone levels, circadian rhythm abnormalities, primary insomnia, mood disorders, coexistent medical conditions, and lifestyle. Exogenous melatonin reportedly induces drowsiness and sleep, and may ameliorate sleep disturbances, including the nocturnal awakenings associated with old age and the menopausal transition. Recently, more potent melatonin analogs with prolonged effects and slow-release melatonin preparations have been developed. The melatonergic receptor ramelteon is a selective melatonin-1 (MT1) and melatonin-2 (MT2) receptor agonist with negligible affinity for other neuronal receptors, including gamma-aminobutyric acid and benzodiazepine receptors. It was found effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT1 and MT2 melatonergic agonism and relatively weak serotonin 5HT2C receptor antagonism, reportedly is effective in the treatment of depression associated insomnia. This article presents the currently available evidence regarding the effects of these compounds on sleep quality and their possible use in menopause associated sleep disturbances.

Effects of exogenous melatonin treatment on out-of-season ram fertility  [cached]
Inmaculada Palacín,José-Alfonso Abecia,Fernando Forcada,Adriana Casao
Italian Journal of Animal Science , 2010, DOI: 10.4081/ijas.2008.199
Abstract: Three field experiments were performed to determine the effects of melatonin implants on the fertility of rams. The experiments were performed on three breeds (Rasa Aragonesa, Assaf and Manchega) in three commercial farms in Spain. Melatonin-treated rams (M) and non-implanted control rams (C) mated either ewes oestrous-induced with FGA intravaginal sponges (Rasa Aragonesa and Assaf farms) or melatonintreated ewes during the anoestrous period (Manchega farm). Scrotal circumference (SC) was measured at melatonin implantation and at ram introduction (nearly 45 d later). Lambing rate, litter size, and fecundity were recorded at parturition. Melatonin implants in rams increased the number of lambs born per ewe in Rasa Aragonesa (19%), Assaf (9%), and Manchega (7%) because of the higher lambing rates exhibited by ewes mated with melatonin-treated rams (Rasa Aragonesa: 80.2% vs 70.5%, P<0.05; Assaf: 74.2% vs 68.0%, NS; Manchega: 90.0% vs 81.5%, P<0.05; for M and C groups, respectively). As a result, the number of extra lambs born per treated ewe was 0.17, 0.10, and 0.10 in the Rasa Aragonesa, Assaf, and Manchega ewes, respectively. In the M and C groups of Rasa Aragonesa rams, mean scrotal circumference increased significantly between the start of the experiments and the onset of mating, but the two groups did not differ significantly at the implantation or at the onset of mating. In the melatonin-treated and control Assaf rams, scrotal circumference increased over the course of the experiments but, at the onset of mating, the melatonin-treated rams had higher SC than did the control rams. Melatonin-treated Manchega rams had scrotal circumferences that were significantly greater than those of the control rams. In the Rasa Aragonesa and Manchega breeds, treating rams using melatonin implants significantly increased the net lamb production of ewes in field conditions. In the Assaf breed, the number of extra lambs born per ewe mated with melatonin treated rams was lower than in the other breeds, even though rams exhibited a significant increase in scrotal circumference. Further research involving the study of semen quality has been planned.
Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission  [PDF]
Sihame Ouakki, Fatima Zahra El Mrabet, Ibtissam Lagbouri, Aboubaker El Hessni, Abdelhalem Mesfioui, Paul Pévet, Etienne Challet, Ali Ouichou
Journal of Behavioral and Brain Science (JBBS) , 2013, DOI: 10.4236/jbbs.2013.37055
Abstract: Recent studies have shown the importance of the GABA-ergic transmission in the pathophysiology of anxiety and depressive disorders in humans. Our present study aims to investigate the interaction of melatonin (MEL) with this system by exploring the effects of MEL with or without a facilitator of GABA-ergic neurotransmission, diazepam (DZ) on the levels of depression and anxiety in Wistar rats. For this purpose, different doses of MEL (2, 4 or 16 mg/kg) or DZ (2 mg/kg) are subchronically administered during 15 days. After pharmacological treatments, anxiety levels are evaluated in behavioral tests of Open Field (OFT) and elevated plus maze (EPM) and depression levels are evaluated by the forced swim test (FST). The results showed that MEL produces anxiolytic-like and antidepressant-like effects in a dose-dependent manner; the maximum effect was obtained at a dose of 16 mg/kg. However, a dose of 4 mg/kg is necessary to induce an effect. The effect of MEL and DZ reported in this study concerns selective modulation of behavioral anxiety and depression since locomotor activity assessed by the OFT and EPM was not affected. The subchronic injection of MEL at 4 mg/kg, DZ at 2 mg/kg or the two combined molecules also induces also anxiety-like and antidepressant-like behavior. In addition, a potentiating effect between MEL and DZ was observed. These effects suggest that psychopharmacological actions of MEL are due, at least in part, to its ability to improve the central GABA-ergic transmission.
Stereological analysis of sciatic nerve in chickens following neonatal pinealectomy: an experimental study
Mehmet Turgut, Süleyman Kaplan, Bur?in ünal, Mehmet Bozkurt, Sinan Yürüker, ?igdem Yenisey, Bünyamin Sahin, Yigit Uyan?kgil, Meral Baka
Journal of Brachial Plexus and Peripheral Nerve Injury , 2010, DOI: 10.1186/1749-7221-5-10
Abstract: The current study investigated the effects of neonatal pinealectomy on the sciatic nerve microarchitecture in the chicken. The chickens were divided into two equal groups: unpinealectomized controls and pinealectomized chickens. At the end of the study, biochemical examination of 10 sciatic nerve samples from both groups was performed and a quantitative stereological evaluation of 10 animals in each group was performed. The results were compared using Mann-Whitney test.In this study, the results of axon number and thickness of the myelin sheath of a nerve fiber in newly hatched pinealectomy group were higher than those in control group. Similarly, surgical pinealectomy group had significantly larger axonal cross-sectional area than the control group (p < 0.05). In addition, the average hydroxyproline content of the nerve tissue in neonatal pinealectomy group was higher than those found in control group. Our results suggest that melatonin may play a role on the morphologic features of the peripheral nerve tissue and that melatonin deficiency might be a pathophysiological mechanism in some degenerative diseases of peripheral nerves. The changes demonstrated by quantitative morphometric methods and biochemical analysis has been interpreted as a reflection of the effects of melatonin upon nerve tissue.In the light of these results from present animal study, changes in sciatic nerve morphometry may be indicative of neuroprotective feature of melatonin, but this suggestion need to be validated in the human setting.Although the injury to the peripheral nervous system is a common clinical problem, a clear understanding of both morphological and pathophysiological alterations associated with this entity is incomplete [1-4]. A basic understanding of specific peripheral nerve biology is critical for the process of nerve degeneration and regeneration. In the clinical setting, the ability to manipulate nerve biology at the cellular level provides a significant improvement in ner
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