Melatonin and Suprachiasmatic Nucleus

 

The Suprachiasmatic nucleus is present in the hypothalamus and is regarded as the pacemaker for the maintenance of the circadian rhythm. Signals from the SCN travels via several multiple synaptic pathways by the involvement of several intrahypothalamic connections for the regulations of circadian rhythm by the secretion of melatonin. Photosensitive melanospin retinal ganglion is activated by light having short wave length and communicate suprachiasmatic nucleus via the retinohypothalamic tract. The neurons of the retinohypothalamic tract release the glutamate and pituitary adenylate cyclase and it activates the polypeptide which mediates the expression of clock gene in the suprachiasmatic nucleus. γ – Aminobutyric neurons of the SCN send direct inhibitory projection to the paraventricular nuclei of the hypothalamus. Neuronal cells of the PVN activate the preganglionic neurons of the intermediolateral cell columns and they are responsible for the control of secretion of the melatonin from the pineal gland. From the amino acid tryptophan, the melatonin is primarily secreted from the pineal gland. The rate by which melatonin synthesis occurs depends upon the neurotransmitter norepinephrine which is responsible for the regulation of arylalkylamie –N-acetyltransferase (AANAT). The AANAT is an enzyme which is responsible for the control of melatonin synthesis. There are two pathways involved in the synthesis and release of melatonin. The first is β1-adrenergic activation and the second is α1 – adrenergic pathways. Incensement of cAMP concentration occurs by the activation of β1 receptor leading to activation of cAMP-dependent PKA. Stimulation of AANAT occurs by the elevated cAMP level and PKA activation. α1 receptor activation leads to incensement of calcium concentration in the intracellular level by the release of calcium ion followed by ca++ influx into the pinealocytes. During the day, the serotonin is stored in pinealocytes and remains unavailable to enzymes. With the onset of darkness, post ganglionic sympathetic outflow to the pineal gland increases which causes the release of NE and the subsequent activation of adrenergic receptors on pinealocytes causes stored serotonin to become accessible for intracellular metabolism. Melatonin is produced by the metabolism of serotonin in two steps which are catalyzed by AANAT or serotonin N-acetyltransferase (SNAT) and hydroxyindole-O-methyltransferase (HIOMT) or acetylserotonin N-methyltransferase (ASMT). N-acetylation of serotonin by AANAT produces N-acetylserotonin (NAS) and O-methylation of NAS by HIOMT, eventually, produces melatonin.

Source:-

Advancing role of Melatonin in the treatment of Neuropsychiatric disorders, Danish Mahmood, Bala Yauri Muhammad,Mahfoudh Alghani, Jamir Anwar, Nasra el labban, Mohammad  Haider,

https://reader.elsevier.com/reader/sd/pii/S2314808X16300197?token=E5A7380C0460B24B2E6026AF99B6B4645D6FBAAED38149AB9BC03F82DB534DBD74A7020525FF217C38D2CD79BD542061&originRegion=eu-west-1&originCreation=20221119123906

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