title: Increased expression of tryptophan-5-hydroxylase 1, but not 2, in brainstem as a result of intrauterine malnutrition.
abstract: The aim of this study was to determine whether intrauterine malnutrition (IUM) produces a change in the expression of tryptophan-5-hydroxylase (TPH) 1 and/or 2 as the primary mechanism to explain the observed chronic cerebral acceleration of the synthesis of 5-hydroxytryptamine (5-HT). We used an IUM model and controls with ages of 1, 15 and 21 days. The brainstem was obtained to determine L-tryptophan, 5-HT and TPH activity. Expression of TPH1 and TPH2 via specific antibodies for each was also evaluated by immunocytochemistry and Western blot. Malnourished offspring had a significant elevation of L-Trp, TPH activity and 5-HT in the brainstem. Both isoforms (1 and 2) of TPH were expressed from birth in both groups; however, TPH1 expression was significantly higher in offspring with IUM in relation to the controls. Importantly, these malnourished offspring showed reduced expression of TPH2 compared to controls. It was confirmed that IUM produces an increase in 5-HT in the brainstem and also showed increased expression of TPH1 at birth, with decreased expression of TPH2. These findings together allow us to propose that chronic elevation of synthesis of 5-HT observed in the brain of the offspring with IUM is probably due to a change in the expression and activity of TPH1 induced from fetal life.
authors: Laboratorio de Patología Molecular, Hospital de Cardiología, Centro Médico Nacional-CMN-SXXI, Instituto Mexicano del Seguro Social-IMSS, México, D.F., Mexico. willisga@prodigy.net.mx
authors: Gabriel
authors: G
authors: Manjarrez-Gutiérrez
authors: Karina
authors: K
authors: Martínez-Radilla
authors: Alfonso
authors: A
authors: Boyzo-Montes de Oca
authors: Sandra
authors: S
authors: Orozco-Suárez
authors: Jorge
authors: J
authors: Hernández-Rodríguez
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D001933:Brain Stem / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D048070:Fetal Nutrition Disorders / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
chemical_list: D012701:Serotonin; D014365:Tryptophan Hydroxylase; C504570:tph1 protein, rat; C504569:tph2 protein, rat