title: [An experimental study on the effects of maternal hyperphenylalaninemia on the central nervous system and behavior of offspring rats].
abstract: OBJECTIVE
  This work attempts to study the cerebral alterations in rat offspring of hyperphenylalaninemic mothers, as well as the possibility of preventing them by means of administration of dietetic supplements of valine, leucine and isoleucine during the pregnancy.
  
  
  METHODS
  An experimental study in two consecutive pregnancies of 18 Wistar rats was carried out. The first pregnancy serves as the control group. In the second pregnancy, an experimental hyperphenylalaninemia was provoked by means of injection of phenylalanine and chlorophenylalanine (phenylalanine-hydroxylase inhibitor). In half of the mothers during the second pregnancy the diet was supplemented with branched-chain amino acids. In the offspring rats, a histological cerebral study was performed (conventional electron microscopy and study of synaptosomes). A behavioral study (T-water maze) was also performed at birth and on the 35th and 65th days of life.
  
  
  RESULTS
  The offspring of the group submitted to hyperphenylalaninemia were microcephalic (p = 0.0003) and had fewer synaptosomes that had a larger surface area (p = 0.0081 in newborn rats, p = 0.0028 on the 35th day of life) and of a more immature aspect (less vesicular content). In addition, alteration in the myelinization were detected. In the behavior test (65th day of life), the offspring of the mothers with hyperphenylalaninemia make significantly more mistakes (p = 0.0167) and they needed more time for their resolution (p = 0.059). None of these alterations could be prevented by the administration of supplements of branched-chain amino acids to the mother. These supplements resulted in a higher fertility rate, but this action results in affected young rats, so their administration seems to be counter-productive.
authors.affiliation: Departamento de Pediatría, Hospital Infantil Miguel Serve, Zaragoza.
authors.forename: C
authors.initials: C
authors.lastname: García Vera
authors.forename: A
authors.initials: A
authors.lastname: Baldellou Vázquez
authors.forename: J
authors.initials: J
authors.lastname: Gracia Romero
authors.forename: P
authors.initials: P
authors.lastname: Ventura Faci
authors.forename: J
authors.initials: J
authors.lastname: Pérez-González
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D010134:Fenclonine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010649:Phenylalanine / Q000008:administration & dosage / Q000494:pharmacology*; D010651:Phenylalanine Hydroxylase / Q000037:antagonists & inhibitors; D017042:Phenylketonuria, Maternal / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000473:pathology
chemical_list: D000597:Amino Acids, Branched-Chain; D004791:Enzyme Inhibitors; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; D010134:Fenclonine
vernacular_title: Estudio experimental sobre los efectos de la hiperfenilalaninemia materna en el sistema nervioso central y la conducta de ratas hijas.