Dihydropteridine reductase activity in the brainstem of intrauterine growth-restricted rats |
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Authors: | Gabriel Manjarrez-Gutierrez Misael Gonzalez-Ramirez Alfonso Boyzo-Montes de Oca Jorge Hernandez-Rodriguez |
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Institution: | 1. Laboratory of Molecular Pathology, Cardiology Hospital, National Medical Center (CMN-SXXI), Mexican Institute of Social Security (IMSS), Mexico City 06725, Mexico;2. Laboratory of Developmental Neurochemistry, Specialties Hospital, CMN-SXXI, IMSS, Mexico City 06725, Mexico;3. Laboratory of Neurontogeny, Department of Physiology, Biophysics and Neurosciences, Center of Research and Advanced Studies (CINVESTAV) IPN, Mexico City 07360, Mexico |
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Abstract: | The aim of this study was to determine whether intrauterine growth restriction produces an increase of dihydropteridine reductase activity as a compensatory mechanism that maintains the necessary concentration of cofactor, tetrahydrobiopterin, during accelerated brain serotonin biosynthesis. Intrauterine growth-restricted offspring and controls were used. On days 1, 10, 15 and 21 of life, the brainstem was dissected and l-tryptophan, serotonin, tryptophan-5-hydroxylase and dihydropteridine reductase activities were determined. Intrauterine growth-restricted pups showed a significant increase of l-tryptophan, 5-hydroxytryptamine, tryptophan-5-hydroxylase and also dihydropteridine activity in the brainstem in comparison to normal pups. These results confirm that intrauterine growth restriction produces an increase of serotonin biosynthesis in the brainstem. This is accompanied by an increase in dihydropteridine activity that appears to be a compensatory mechanism to maintain sufficient tetrahydrobiopterin for the donation of electrons during the accelerated synthesis of brain serotonin in intrauterine growth-restricted rats. |
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Keywords: | IUGR intrauterine growth restriction 5-HT 5-Hydroxytryptamine BH4 tetrahydrobiopterin l-Trp l-tryptophan Tph tryptophan-5-hydroxylase 5-HTP 5-hydroxytryptophan GTP guanosine triphosphate NADPH nicotinamide adenine dinucleotide reduced DHPR dihydropteridine reductase |
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