Developmental effects of intrauterine growth retardation on cerebral amino acid transport

Abstract

Early restriction of nutrients during the perinatal period of life can modify the development of the mammalian fetus and have marked repercussions on the ontogeny of the CNS. The brain is vulnerable to undernutrition, with delayed morphologic and biochemical maturation leading to impaired functions. The aim of the present investigation was to assess whether modified brain neurotransmitter and amino acid concentrations found in an animal model of intrauterine growth retardation were related to modified blood-brain amino acid transport properties. Four amino acids were tested: alanine and taurine, plus two neurotransmitter precursors, tryptophan and tyrosine. Intrauterine growth retardation was induced by restriction of maternal-fetal blood flow from the 17th d of gestation. Blood-brain transport of these amino acids was measured by i.v. injection of radiolabeled amino acids in 7-d-old, 21-d-old, and 60-d-old intrauterine growth-retarded or control rats. No major statistical differences were revealed either for brain regional transport or between intrauterine growth-retarded animals and controls at any age studied. Transfer coefficients and influxes remained statistically similar for almost all brain regions in both groups. A significant decrease and different time course for amino acid transport with age related to the blood-brain barrier maturation are confirmed in this model. Our results are related to a major role of the blood-brain barrier as a part of mechanisms leading to "brain growth sparing."