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Description:
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Melatonin is rhythmically synthesized and released by the pineal gland and , in some species , retina during the night and regulates many physiological and behavioral processes in birds and mammals . Chick diencephalic astrocytes express two melatonin receptor subtypes in vitro , and melatonin plays a role in regulating metabolic activity . We examined the role of glial cells in circadian function and asked if melatonin modulated glial functions within the retina and the brain . Calcium waves were potentiated by physiological concentrations of melatonin . Melatonin increased resting calcium levels and reduced gap junctional coupling among astrocytes at these same concentrations . Both mouse and chick diencephalic and telencephalic astrocytes express melatonin receptor protein . Nanomolar melatonin modulated astrocytic calcium waves of the mouse and chick diencephalon but not waves of the telencephalon . Mammalian intercellular calcium waves spread farther than avian calcium waves , and the nature of the spread of the waves differed between telencephalic and diencephalic mammalian astrocytes . These differences in propagation were abolished by melatonin . Using northern analysis , we identified period2 , period3 , cryptochrome1 , cryptochrome2 , clock , melanopsin and peropsin within chick diencephalic astrocytes . The clock genes cry1 and , per2 were expressed rhythmically in a LD cycle , but metabolic activity was not rhythmic . When cells were placed in constant darkness and rhythmically administrated melatonin , a robust rhythm in glucose uptake was induced without a coordinated clock gene rhythm , suggesting rhythmic clock gene expression and metabolic activity are separable processes . Melatonin affected visual function as assessed by electroretinogram . Circadian rhythms of a - and b -wave implicit times and amplitudes were observed . Melatonin (1 mg /kg and 100 ng /kg ) decreased a - and b -wave amplitudes greater during the night than during the day and it increased a - and b -wave implicit times while 1 ng /kg melatonin had little to no effect over the saline controls . These data indicate that melatonin modulates glial intercellular communication , affects metabolic activity in astrocytes , and may play a role in regulating a day and night functional shift in the retina , at least partially through Müller glial cells . Thus , melatonin can regulate glia function and thereby , affect outputs of the vertebrate biological clock . |