Abstract
The suprachiasmatic nucleus (SCN) is the master circadian pacemaker. The pineal hormone melatonin is involved in the regulation of circadian phase. As a part of the circadian system, its synthesis and secretion is under SCN control. On the other hand, melatonin feeds back on the SCN to regulate its function. Melatonin has two specific windows of time at which it regulates SCN function, namely dusk and dawn. It has been suggested that melatonin exerts its effect on the SCN during that specific window of time via one or both of its specific receptors, MT1 or MT2. The hypothesis that the density of these receptors varies across the circadian cycle was tested. Using immunohistochemistry with receptor-specific antibodies, the localization and distribution of melatonin receptors MT1 and MT2 was studied in the SCN at different Zeitgeber times (ZT): ZT 11–13 (dusk), 23–01 (dawn), 5–7 (mid-day), and 17–19 (midnight). Our results show that MT1 receptor density significantly increased at dusk relative to dawn and midnight (p<0.01 and p<0.001 respectively). Although MT1 receptors were widespread in the SCN and parts of the optic chiasm at dusk, they were restricted to the SCN during the mid-day period. MT2 receptors were not detected in the SCN. Thus, we find that melatonin receptor MT1 density and distribution varies with circadian time. This creates a time window during which melatonin can affect the operation of the SCN. We also find that melatonin regulates SCN function via MT1 receptors with a minimal role for MT2.
Highlights
Melatonin, “the chemical expression of darkness” [20], is a neuroendocrine hormone synthesized and secreted by the pineal gland [4,25]
When the pattern of labeling for MT1 receptors within the suprachiasmatic nucleus (SCN) was examined across the circadian cycle, MT1 receptors were detected within the SCN at dusk (ZT 11–13) (Fig. 3)
The results of this study show that the localization and distribution of melatonin receptors MT1 is regulated in a circadian mode in rat SCN
Summary
“the chemical expression of darkness” [20], is a neuroendocrine hormone synthesized and secreted by the pineal gland [4,25]. There is a circadian rhythm in melatonin synthesis and secretion that peaks at night and troughs during the day [20]. The circadian rhythm of melatonin synthesis is driven by the intrinsic circadian activity of the suprachiasmatic nucleus (SCN). This small paired nucleus in the anterior hypothalamus is entrained to a 24-hour period by the light/dark cycle (LD) [14]. Melatonin feeds back on the SCN to regulate its function by modulation of SCN electrical activity [11,12], resetting the clock [5,6] and synchronizing locomotor activity [17,19,24]. Melatonin can reset the circadian clock only at temporally distinct times, dusk and dawn. When melatonin is administered at dusk, it phase advances the firing rate of SCN neurons in rat and mouse
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