Evidence for melatonin synthesis in the rat brain during development

Abstract

Melatonin production is not restricted to the pineal gland. Several extrapineal sources of this indole such as retina, Harderian gland, and immune system are well documented. Melatonin of pineal origin is not present in the rat at early stages of development. To assess the potential capacity of local melatonin synthesis by the immature brain and to gain insight into the relationship between melatonin production by the brain (without the pineal gland) and pineal gland during rat development, the melatonin content as well as the expression and activity of the melatonin-synthesizing enzymes, N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), were studied at fetal and postnatal stages. Moreover, melatonin-membrane receptor (MT(1)) expression was also analyzed. Both, the expression and activity of NAT and HIOMT were found in the brain with significant day/night differences in enzymes activities. Additionally, melatonin content was detected in all stages showing day/night differences depending on the stage of development. The brain nocturnal melatonin content was higher than diurnal content on postnatal day 16 and in adult rats which is in accordance with the pineal melatonin synthesis. To investigate the origin of this brain melatonin, pinealectomized rats were used and we found that the developing brain produced its own melatonin. Also, MT(1) expression was detected in brain during development. These results demonstrate that, when the pineal is not yet producing melatonin, there is melatonin synthesis by the brain that could be used as protection from free radical damage and/or could exert some actions through MT(1) receptors.

Long-term melatonin administration enhances the antioxidant potential of human plasma maintained after discontinuation of the treatment

“…Melatonin (N-acetyl-5-methoxytryptamine) is an endogenously-produced indol found in the pineal gland as well as in several extra pineal tissues such as retina, gastrointestinal tract and some cerebral structures (Karasek and Winczyk 2006;Jimenez-Jorge et al 2007), which regulates many physiological functions ). Since 1991, melatonin has been known as a powerful endogenic antioxidant and radical scavenger (Ianas et al 1991).…”

Melatonin combats molecular terrorism at the mitochondrial level

“…Within multicellular organisms melatonin is generated in a wide variety of different tissues, although the pineal gland is the best known source of the indoleamine in vertebrates (Quay, 1974; Reiter, 1991b). Other major sites of melatonin production include the eye (Tosini et al ., 2006; Itoh et al ., 2007), brain (Jimenez-Jorge et al ., 2007), gut (Bubenik and Pang, 2007), bone marrow (Tan et al ., 1999a), skin (Slominski et al ., 2005), immune cells (Carrillo-Vico et al ., 2005) and others (Stefulj et al ., 2001). In mammals, melatonin in the blood is primarily derived from the pineal gland (Quay, 1974; Reiter, 1991a).…”

Melatonin signaling in mouse cerebellar granule cells with variable native MT1 and MT2 melatonin receptors

“…The nanomolar concentrations of melatonin act on the G protein-coupled melatonin receptors MT1 and MT2 (formerly known as Mel1a and Mel1b) (Dubocovich et al, 2003;Witt-Enderby et al, 2006). These receptors, which typically are linked to the inhibition of cAMP-mediated signaling, are expressed in various types of mammalian neurons including in the human brain (Brunner et al, 2006;Jimenez-Jorge et al, 2007;Savaskan et al, 2002Savaskan et al, , 2005Thomas et al, 2002;Uz et al, 2005;Wu et al, 2006Wu et al, , 2007. The pattern of MT1 and MT2 expression appears to be cell-type specific and species-dependent.…”