Hypoglycemia alters striatal amino acid efflux in perinatal rats: An in vivo microdialysis study

Abstract

In adult brain, during insulin-induced hypoglycemia, striatal extracellular fluid concentrations of the excitatory amino acids glutamate and aspartate rise markedly (fourfold to tenfold). In this study, we used in vivo microdialysis to determine if insulin-induced hypoglycemia altered striatal amino acid efflux in similar fashion in the immature brain. Microdialysis probes were inserted into the right striatum of rats on postnatal day 7. After a 2-hour recovery period, in each animal a 30-minute baseline sample was obtained. Then insulin (0.6 Μ/Kg, intraperitoneal injection) was administered (n = 6) and dialysate sampling was continued over the next 210 minutes (terminal blood glucose level < 5 mg/dl). Untreated control rats (n = 6) were sampled over the same time interval. After pre-column derivatization with o -Phthaldialdehyde, dialysate samples were assayed by high-pressure liquid chromatography with electrochemical detection to measure their amino acid content; eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine glycine, and asparagine) were consistently detected. In controls, amino acid efflux did not change over 4 hours. In hypoglycemic animals, glutamate efflux increased (peak: 238 ± 85% of baseline, p = 0.02, repeated measures analysis of variance [ANOVA]), glutamine efflux declined (to 44 ± 5% of baseline, P = 0.002, ANOVA), and taurine efflux increased (up to 310 ± 120% of baseline; p < 0.06, ANOVA). In contrast with 9-to 12-fold increases in aspartate efflux reported in adult striatum, asparate efflux increased only slighty (to 174 ± 69% of baseline; not significant). In immature rodent brain, overall trends in striatal amino acid efflux during hypoglycemia are similar to patterns reported in adult animals; however, there are major differences in the timing, duration, and magnitude of these responses.