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Developmental effects of intrauterine growth retardation on cerebral amino acid transport
O Rabin1, J M Lefauconnier, C Chanez
1Laboratoire INSERM U 26, Unité de Neurotoxicologie, Hôpital Fernand WIDAL, Paris, France.
Insights
Early life nutrient restriction impacts fetal development. This study found blood-brain barrier amino acid transport remained largely unchanged in growth-restricted rats, suggesting a protective role for the barrier in sparing brain growth.
Area of Science:
- Neuroscience
- Developmental Biology
- Physiology
Background:
- Perinatal nutrient restriction can negatively affect central nervous system (CNS) development.
- Undernutrition during critical developmental windows impairs brain maturation and function.
- Intrauterine growth retardation (IUGR) may alter brain amino acid and neurotransmitter levels.
Purpose of the Study:
- To investigate if altered brain amino acid concentrations in an IUGR animal model correlate with changes in blood-brain amino acid transport.
- To assess the transport of alanine, taurine, tryptophan, and tyrosine across the blood-brain barrier in IUGR rats.
Main Methods:
- IUGR was induced by restricting maternal-fetal blood flow in rats from day 17 of gestation.
- Blood-brain transport of radiolabeled amino acids (alanine, taurine, tryptophan, tyrosine) was measured in IUGR and control rats at 7, 21, and 60 days of age.
- Transport was assessed across various brain regions.
Main Results:
- No significant differences in regional blood-brain transport rates (transfer coefficients, influxes) were observed between IUGR and control rats at any age.
- Age-related changes in amino acid transport, reflecting blood-brain barrier maturation, were confirmed in both groups.
- Transport parameters remained statistically similar across most brain regions in both IUGR and control animals.
Conclusions:
- The blood-brain barrier appears to maintain consistent amino acid transport properties despite intrauterine growth retardation.
- These findings suggest the blood-brain barrier plays a crucial role in protecting the developing brain, contributing to "brain growth sparing" mechanisms.
- The study highlights the resilience of blood-brain barrier transport function in the context of developmental undernutrition.
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."