Differential Amino Acid Uptake into Cerebral Parenchyma and Capillary Cells during Development

Abstract

The amino acids aspartate, glutamate and glycine are neurotransmitters within the central nervous system1. High, uncontrolled brain levels of these amino acids is potentially harmful2,3 therefore entry into the brain must be carefully controlled in the face of plasma elevations. This is accomplished by the blood-brain barrier (BBB). In general, neutral amino acid uptake into brain is high in the immature animal4 due to the a greater demand for protein synthesis of the developing brain5. In our recent studies, we have demonstrated that the neurotransmitter amino acids also show greater uptake into the neonatal brain compared to the adult6,7. It is possible that this high brain uptake is due to endothelial cell trapping of amino acid since the neonatal BBB contains many vesicles which are not seen in adults8. To investigate the contribution of endothelial cell sequestration to neonatal brain amino acid, we have combined the in situ brain perfusion technique with dextran density capillary depletion. This combination allows the differential uptake of amino acid into brain and capillary endothelium to be measured.