Release of Endogenous Amino Acids from the Hippocampus and Brain Stem from Developing and Adult Mice in Ischemia

Abstract

The release of neurotransmitters and modulators has been studied mostly using labeled preloaded compounds. For several reasons, however, the estimated release may not reliably reflect the release of endogenous compounds. The basal and K(+)-evoked release of the neuroactive endogenous amino acids GABA, glycine, taurine, L-glutamate and L-aspartate was now studied in slices from the hippocampus and brain stem from 7-day-old and 3-month-old mice under control and ischemic conditions. The release of synaptically not active L-glutamine, L-alanine, L-threonine and L-serine was assessed for comparison. The estimates for the hippocampus and brainstem were markedly different and also different in developing and adult mice. GABA release was much greater in 3-month-old than in 7-day-old mice, whereas with taurine the situation was the opposite, in the hippocampus in particular. K(+) stimulation enhanced glycine release more in the mature than immature brain stem while in the hippocampus the converse was observed. Ischemia enhanced the release of all neuroactive amino acids in both brain regions, the effects being relatively most pronounced in the case of GABA, aspartate and glutamate in the hippocampus in 3-month-old mice, and taurine in 7-day-old and glycine in 3-month-old mice in the brain stem. These results are qualitatively similar to those obtained on earlier experiments with labeled preloaded amino acids. However, the magnitudes of the release cannot be quite correctly estimated using radioactive labels. In developing mice only taurine release may counteract the harmful effects of excitatory amino acids in ischemia in both hippocampus and brain stem.

Glycine Exerts Dual Roles in Ischemic Injury Through Distinct Mechanisms

“…4,5 Glycine is a 2-faceted bioactive molecule in the central nervous system. 6 Glycine is a strychnine-insensitive coagonist for N-methyl-D-aspartate receptors (NMDAR) and is essential for activation of NMDARs.…”

Release of Endogenous Amino Acids from the Striatum from Developing and Adult Mice in Ischemia

“…These changes seem to be somewhat dissimilar in different brain regions. For instance, in the brain stem glutamate and GABA decrease during postnatal development and there is no marked change in GABA in the hippocampus [28]. There occurred no measurable increase in the extrusion of lactate dehydrogenase (a common marker of plasma membrane damage and nonspecific lysis of neural cells) from the slices upon incubation in ischemia (data not shown).…”

Glycine release provoked by disturbed Na+, K+ and Ca2+ homeostasis in cerebellar nerve endings: roles of Ca2+ channels, Na+/Ca2+ exchangers and GlyT2 transporter reversal

“…Monitoring glycine release in different CNS preparations has proven to be more difficult than in the case of other neurotransmitters for a number of reasons. The multiple sources of extracellular glycine, which can be released from neurons and glia besides being a metabolic ingredient, may make the monitoring of endogenous glycine in the extracellular fluids an index of difficult interpretation (but see Oja and Saransaari 2009). However, the analysis of the efflux of radioactive glycine pre‐accumulated into CNS tissues has not been as satisfactory as expected, largely because glycine can be captured also by structures other than glycinergic neurons, through two distinct transporters termed GlyT1 and GlyT2 (see López‐Corcuera et al.…”