title: Unique Regulation of the Melatonin Synthetic Pathway in the Retina of Diurnal Female Arvicanthis ansorgei (Rodentia).
abstract: Knowledge about melatonin synthesis and its potential roles within the retina remains fragmented, especially in mammals where studies have focused on the penultimate enzyme of melatonin synthesis arylalkylamine N-acetyltransferase (AA-NAT), whereas the final enzyme necessary for melatonin production is hydroxyindole-O-methytransferase (HIOMT). We explored multiple parameters of the melatonin synthetic pathway in the cone-rich retina of a diurnal rodent, Arvicanthis ansorgei, cones being previously implicated as probable reservoirs of melatonin production. We analyzed the temporal and spatial expression of Aa-nat mRNA and AA-NAT protein and enzymatic activity of AA-NAT, HIOMT, as well as the melatonin receptor type 1 and melatonin itself. We report that Aa-nat mRNA was localized principally to cones and ganglion cells (retinal ganglion cell [RGC]) with opposing cyclic expression, being maximal in cones during the night, and maximal in RGC in the daytime. AA-NAT protein was also immunolocalized to these same populations, and was present and active throughout the 24-hour period. HIOMT immunolocalization mirrored that of AA-NAT, but expression levels and activity were extremely low and remained uniform throughout the 24-hour period. MT1 showed a complementary expression pattern to the synthetic enzymes, present in rod photoreceptors, some inner retinal neurons and RGC. Surprisingly, melatonin levels were consistently low throughout the day/night cycle, in accordance with the low activity levels of HIOMT. These data demonstrate that the melatonin synthetic pathway in a diurnal rodent differs from that described for other tissues and species (nocturnal and diurnal), the contrasting phase expression in photoreceptors and RGC, suggesting distinct roles in these populations.
authors.affiliation: Centre National de la Recherche Scientifique Unité Propre de Recherche 3212 (C.G., D.H., V.L.), Institute for Cellular and Integrative Neurosciences, F-67084 Strasbourg, France; Centre National de la Recherche Scientifique Unité Mixte de Recherche 7364 (D.C.), Laboratoire de Neurosciences Cognitives et Adaptatives, Université de Strasbourg, Faculté de Psychologie, F-67000 Strasbourg, France; and Department of Pharmacology and Toxicology (G.T.), Morehouse School of Medicine, Atlanta, Georgia 30110.
authors.forename: Coralie
authors.initials: C
authors.lastname: Gianesini
authors.affiliation: Centre National de la Recherche Scientifique Unité Propre de Recherche 3212 (C.G., D.H., V.L.), Institute for Cellular and Integrative Neurosciences, F-67084 Strasbourg, France; Centre National de la Recherche Scientifique Unité Mixte de Recherche 7364 (D.C.), Laboratoire de Neurosciences Cognitives et Adaptatives, Université de Strasbourg, Faculté de Psychologie, F-67000 Strasbourg, France; and Department of Pharmacology and Toxicology (G.T.), Morehouse School of Medicine, Atlanta, Georgia 30110.
authors.forename: Daniel
authors.initials: D
authors.lastname: Clesse
authors.affiliation: Centre National de la Recherche Scientifique Unité Propre de Recherche 3212 (C.G., D.H., V.L.), Institute for Cellular and Integrative Neurosciences, F-67084 Strasbourg, France; Centre National de la Recherche Scientifique Unité Mixte de Recherche 7364 (D.C.), Laboratoire de Neurosciences Cognitives et Adaptatives, Université de Strasbourg, Faculté de Psychologie, F-67000 Strasbourg, France; and Department of Pharmacology and Toxicology (G.T.), Morehouse School of Medicine, Atlanta, Georgia 30110.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tosini
authors.affiliation: Centre National de la Recherche Scientifique Unité Propre de Recherche 3212 (C.G., D.H., V.L.), Institute for Cellular and Integrative Neurosciences, F-67084 Strasbourg, France; Centre National de la Recherche Scientifique Unité Mixte de Recherche 7364 (D.C.), Laboratoire de Neurosciences Cognitives et Adaptatives, Université de Strasbourg, Faculté de Psychologie, F-67000 Strasbourg, France; and Department of Pharmacology and Toxicology (G.T.), Morehouse School of Medicine, Atlanta, Georgia 30110.
authors.forename: David
authors.initials: D
authors.lastname: Hicks
authors.affiliation: Centre National de la Recherche Scientifique Unité Propre de Recherche 3212 (C.G., D.H., V.L.), Institute for Cellular and Integrative Neurosciences, F-67084 Strasbourg, France; Centre National de la Recherche Scientifique Unité Mixte de Recherche 7364 (D.C.), Laboratoire de Neurosciences Cognitives et Adaptatives, Université de Strasbourg, Faculté de Psychologie, F-67000 Strasbourg, France; and Department of Pharmacology and Toxicology (G.T.), Morehouse School of Medicine, Atlanta, Georgia 30110.
authors.forename: Virginie
authors.initials: V
authors.lastname: Laurent
mesh_terms: D000121:Acetylserotonin O-Methyltransferase / Q000378:metabolism; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D002940:Circadian Rhythm; D005260:Female; D008550:Melatonin / Q000096:biosynthesis*; D051189:Murinae / Q000378:metabolism*; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*
chemical_list: D044122:Receptor, Melatonin, MT1; D000121:Acetylserotonin O-Methyltransferase; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin