AIMTo observe the role of melatonin receptor and GABAA receptor in sleeping time prolonged by melatonin in mice.

METHODSThe absence of the righting reflex was considered as the sleep onset and the duration of the loss of the righting reflex was recorded as the sleeping time. The effects of receptor agonist and antagonist on hypnotic activity of melatonin were studied in the paper.

RESULTSPrazosin hydrochloride, the blocker of melatonin 3 receptor, didn't affect the sleeping time prolonged by melatonin in mice. GABA, the endogenous agonist of GABA receptor, significantly potentiated the hypnotic activity of melatonin. When picrotoxin, the ligand of picrotoxin site on GABAA receptor, used together with melatonin, it significantly antagonized the sleeping time prolonged by melatonin, however, bicuculline, the specific antagonist of GABA binding site in GABAA receptor, didn't affect the hypnotic activity of melatonin in mice.

CONCLUSIONMelatonin does not exhibit its potentiation sleeping time in mice through melatonin 3 receptor. Hypnotic activity of melatonin may be mediated through picrotoxin site on GABAA receptor.

Animals ; Bicuculline ; pharmacology ; Male ; Melatonin ; physiology ; Mice ; Mice, Inbred Strains ; Picrotoxin ; pharmacology ; Prazosin ; pharmacology ; Receptors, GABA-A ; physiology ; Receptors, Melatonin ; physiology ; Sleep ; physiology

OBJECTIVE: To study the effect of different melatonin treatment regimens on long-term behavior and white matter damage in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to seek an optimal melatonin treatment regimen. METHODS: Healthy Sprague-Dawley rats, aged 7 days, were randomly divided into four groups: sham-operation, HIBD, single-dose immediate treatment (SDIT), and 7-day continuous treatment (7DCT), with 8 rats in each group. A neonatal rat model of HIBD was prepared according to the classical Rice-Vannucci method. On day 21 after HIBD, the Morris water maze test was used to evaluate spatial learning and memory abilities. On day 70 after HIBD, immunofluorescence assay was used to measure the expression of neuronal nuclear antigen (NeuN) in the cerebral cortex and the hippocampal CA1 region of neonatal rats, and double-label immunofluorescence was used to measure the expression of myelin basic protein (MBP) and neurofilament 200 (NF200) in the corpus striatum and the corpus callosum. RESULTS: The results of the Morris water maze test showed that the SDIT and 7DCT groups had a significantly shorter mean escape latency than the HIBD group, and the 7DCT group had a significantly shorter mean escape latency than the SDIT group ( CONCLUSIONS Both SDIT and 7DCT can improve long-term behavior and reduce white matter damage in neonatal rats with HIBD, and 7DCT is more effective than SDIT.
Animals ; Animals, Newborn ; Hypoxia-Ischemia, Brain/drug therapy* ; Melatonin/pharmacology* ; Rats ; Rats, Sprague-Dawley ; White Matter

OBJECTIVE: To investigate the effects of melatonin on the growth and metastasis of MDA-MB-231 breast cancer cells and explore the mechanism. METHODS: MDA-MB-231 cells were treated with 1, 3 or 5 mmol/L melatonin, and the changes in cell proliferation were examined using CCK-8 assay. Colony-forming assay and wound healing assay were used to assess the effects of melatonin treatmnent on colony-forming ability and migration of the cells. Flow cytometry and immunofluoresnce assay were employed to examine apoptosis and positive staining for autophagy-related proteins in the cells treated with 3 mmol/L melatonin. The effects of melatonin treatment alone or in combination with 3-methyladenine (3-MA) on the expressions of the proteins associated with autophagy (LC3, P62 and Beclin1), apoptosis (Bcl2 and Bax) and epithelial-mesenchymal transition (E-cadherin and Snail) were examined with Western blotting. RESULTS: Melatonin treatment significantly inhibited the proliferation of breast cancer cells in a concentration- and time-dependent manner (P < 0.05), suppressed colony-forming ability and migration (P < 0.01), and promoted apoptosis of the cells (P < 0.01). Melatonin treatment alone significantly increased the expressions of Bax (P < 0.05), E-cadherin, LC3-II/LC3-I, and Beclin1 and lowered the expressions of Bcl2 (P < 0.05), Snail, P62 (P < 0.05), and Bcl2/Bax ratio (P < 0.01) in the cells, and caused enhanced positive staining of Beclin1 protein and attenuated staining of P62 protein. Compared with melatonin treatment alone, melatonin treatment combined with 3-MA significantly decreased the expressions of Beclin1 (P < 0.001), LC3-II/LC3-I (P < 0.05), Bax (P < 0.01), and E-cadherin (P < 0.001) and increased the expressions of Bcl2 (P < 0.05), Snail, and Bcl2/Bax ratio (P < 0.01). CONCLUSION Melatonin can induce autophagy of MDA-MB-231 breast cancer cells to inhibit cell proliferation and metastasis and promote cell apoptosis, and suppressing autophagy can weaken the inhibitory effect of melatonin on the growth and metastasis of breast cancer cells.
Autophagy ; Autophagy-Related Proteins/metabolism* ; Breast Neoplasms ; Cell Line, Tumor ; Female ; Humans ; Melatonin/pharmacology*

Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.
Animals ; Female ; Melatonin/pharmacology* ; Ovarian Follicle ; Oocytes ; Granulosa Cells/physiology* ; Mammals

Animals ; Cytokines ; physiology ; Humans ; Immune System ; drug effects ; physiology ; Melatonin ; pharmacology ; Opioid Peptides ; physiology ; Receptors, Melatonin ; physiology ; Stress, Physiological ; immunology ; T-Lymphocytes ; drug effects ; physiology

AIMThe effect and possible mechanism of Melatonin (MEL) on firing rate of pain neurons in lateral habenular nucleus of rats were investigated in the experiment.

METHODSSingle extracellular firing were recorded to study the firing rate changes of pain neurons and sensitivity changes to pain stimulation induced by MEL in LHb of rats. Reverse effect of naloxone on the analgesia induced by melatonin was also observed.

RESULTSMelatonin showed the effects on the firing of pain neurons in the LHb and decreased the sensitivity of pain neurons to pain stimulation, which could be reversed by naloxone.

CONCLUSIONMelatonin can change the responses of pain neurons to pain stimulation via opioid receptor in the LHb, which might be one of analgesic mechanisms by MEL.

Analgesics ; pharmacology ; Animals ; Habenula ; drug effects ; physiology ; Male ; Melatonin ; pharmacology ; Neuralgia ; physiopathology ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar

OBJECTIVE: To investigate the effect of melatonin (MLT) on the proliferation and apoptosis of human multiple myeloma cell line RPMI 8226 and its possible mechanism. METHODS: RPMI 8226 cells were cultured in vitro, and different concentrations of MLT were treated on RPMI 8226 cells. The effects of MLT on RPMI 8226 cell proliferation were detected by CCK-8 assay and methylcellulose cloning assay, and the effects of MLT on cell apoptosis were detected by AnnexinV-FITC /PI, flow cytometry. Western blot was used to determine the expression of apoptosis and endoplasmic reticulum stress-related proteins in each group, and CCK-8 assay was used to determine the effect of MLT combined with bortezemib on the viability of RPMI 8226 cells. RESULTS: MLT inhibited the proliferation of RPMI 8226 cells in a dose- and time-dependent manner (r=-0.9777，r=-0.9951). With the increase of MLT concentration, the number of clones decreased, the apoptosis of RPMI 8226 cells increased (P<0.05), the expression of anti-apoptotic protein XIAP decreased, the expression of apoptotic proteins Bax and Caspase3 increased, and the expression of endoplasmic reticulum stress-related proteins increased. Compared with the control group, the survival of RPMI 8226 cells in the MLT and BTZ combined group significantly decreased (P<0.01). CONCLUSION MLT can inhibit the proliferation of RPMI 8226 cells, promote the apoptosis of RPMI 8226 cells, and enhance the anti-tumor effect of BTZ on RPMI 8226 cells. The mechanism may be related to endoplasmic reticulum stress.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Endoplasmic Reticulum Stress ; Humans ; Melatonin/pharmacology* ; Multiple Myeloma/pathology* ; Sincalide/pharmacology*

OBJECTIVETo study serum levels of melatonin in children with epilepsy or febrile seizures in order to provide a basis for the treatment of epilepsy or febrile seizures with melatonin.

METHODSSerum melatonin levels were measured using ELISA in 15 children with simple febrile seizure (SFS), in 15 children with complex febrile seizure (CFS), in 15 children with epilepsy, and in 15 children with upper respiratory infections (control group).

RESULTSSerum melatonin levels in children with epilepsy (8.66+/-1.38 ng/L) or CFS (14.91+/-2.61 ng/L) were significant lower than those in the control group (23.93+/-2.01 ng/L) (P<0.01). The SFS group showed lower serum melatonin levels (20.72+/-2.54 ng/L) compared with the control group, but there were no statistical differences between the two groups. Serum melatonin levels in the epilepsy group were significantly lower than those in the CFS (P<0.05) and the SFS groups (P<0.01).

CONCLUSIONSSerum melatonin levels decreased in children with epilepsy or CFS. Supplement of exogenous melatonin might be a promising treatment for epilepsy and febrile seizures in children.

Child ; Child, Preschool ; Epilepsy ; blood ; drug therapy ; Female ; Humans ; Infant ; Male ; Melatonin ; blood ; pharmacology ; therapeutic use ; Seizures, Febrile ; blood

AIMTo study whether melatonin has effect on oocyte maturation of mouse in vitro.

METHODSMouse oocytes were cultured in maturation medium, HX-medium, or HX-medium supplemented with FSH, and the effects of MT on meiotic maturation of mouse oocyte were examined.

RESULTS(1) MT at all doses of 0.1 g/L, 0.02 g/L, 0.4 g/L or 0.8 g/L inhibited the formation of PB1 in CEO cultured in maturation medium and had no effect on GVBD. (2) MT could delay GVBD and the extrusion of PB1 in CEOs of mouse oocytes by dynamic curves. In contrast to the control, GVBD and PB1 extrusion of oocytes in the treated groups had been delayed by 8-10 hours and 3-4 hours respectively. (3) MT inhibited the effect of FSH on resumption of meiosis, but no effect on the formation of PB1. (4) MT and HX had cooperation effects on spontaneous oocyte maturation in CEO, but not in DO.

CONCLUSIONMT is able to affect mouse oocyte maturation and the regulation mechanisms may be related to cumulus cells.

Animals ; Female ; In Vitro Oocyte Maturation Techniques ; Melatonin ; pharmacology ; Mice ; Mice, Inbred Strains ; Oocytes ; drug effects ; physiology ; Oogenesis ; drug effects

AIMTo investigate effects of melatonin on estrogen receptor at the primary stage of melatonin (MLT) inhibiting the proliferation of 17-beta-estradiol (E2)-induced pituitary prolactin-secreting tumor (prolactinoma) and its mechanisms in the rat.

METHODSMLT inhibiting the proliferation of 17-beta-E2-induced prolactinoma was created by administrating different concentration of melatonin subcutaneously at 18:00 in every group of SD rat in vivo. We also examined the expression of MLT receptor in prolactinoma cells and the effects of MLT on the expression of estrogen receptor (ER) by in situ hybridization and the effects of MLT on the binding of ER to estrogen response element (ERE) by electrophoretic mobility shift assay (EMSA)in primary culture cells iv vitro.

RESULTSThe results showed that the weights of prolactinomas in MLT groups, in which 0.25 mg or 0.50 mg/day/rat melatonin was administrated subcutaneously at 18:00, were decreased significantly (P < 0.01 and P < 0.05). The expression of MLT1a and MLT1b were shown in pituitary prolactinoma cells. Compared with the prolactinoma, the expression of ER and the bind of ER to ERE in prolactinoma treated with 0.25 mg/day/rat or 0.50 mg/day/rat MLT was decreased (P < 0.01 and P < 0.01).

CONCLUSIONThese data indicate that some dosage of MLT inhibit the development of E2-induced prolactinoma in SD rat. One of the mechanisms is involved in suppressing the expression of estrogen receptor and partly inhibiting the bind of ER to ERE.

Animals ; Estradiol ; pharmacology ; Male ; Melatonin ; pharmacology ; Pituitary Neoplasms ; pathology ; Prolactinoma ; pathology ; Rats ; Rats, Sprague-Dawley ; Receptors, Estrogen ; drug effects ; Response Elements