Ischemia Induces Release of Endogenous Amino Acids from the Cerebral Cortex and Cerebellum of Developing and Adult Mice

Simo S Oja,Pirjo Saransaari

doi:10.1155/2013/839036

Simo S Oja, Pirjo Saransaari

Open Access

https://doi.org/10.1155/2013/839036

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Abstract

Ischemia enhanced release of endogenous neuroactive amino acids from cerebellar and cerebral cortical slices. More glutamate was released in adult than developing mice. Taurine release enhanced by K+ stimulation and ischemia was more than one magnitude greater than that of GABA or glutamate in the developing cerebral cortex and cerebellum, while in adults the releases were almost comparable. Aspartate release was prominently enhanced by both ischemia and K+ stimulation in the adult cerebral cortex. In the cerebellum K+ stimulation and ischemia evoked almost 10-fold greater GABA release in 3-month olds than in 7-day olds. The release of taurine increased severalfold in the cerebellum of 7-day-old mice in high-K+ media, whereas the K+-evoked effect was rather small in adults. In 3-month-old mice no effects of K+ stimulation or ischemia were seen in the release of aspartate, glycine, glutamine, alanine, serine, or threonine. The releases from the cerebral cortex and cerebellum were markedly different and also differed between developing and adult mice. In developing mice only the release of inhibitory taurine may be large enough to counteract the harmful effects of excitatory amino acids in ischemia in both cerebral cortex and cerebellum, in particular since at that age the release of glutamate and aspartate cannot be described as massive.

Highlights

Glutamate and γγ-aminobutyrate (GABA) are the two major amino acid transmitters in the cerebral cortex and cerebellum, glutamate being responsible for excitatory and GABA for inhibitory transmission [1]
E excessive extracellular accumulation of excitatory amino acids, predominantly that of glutamate and of aspartate, in ischemia leads to cellular damage in the brain [6, 7]. eir massive release activates glutamate receptors, in particular those of the NMDA class [8], which leads to an excessive in ux of Ca2+ and consequent adverse effects [9]. is excitotoxicity may be counteracted by the simultaneous enhanced release of inhibitory GABA and taurine [10, 11]. e functional status in the brain is a delicate balance between these excitatory and inhibitory neurotransmitters under both normal and pathological conditions
The calculated release rate is affected by the efficacy of this mixing and the sizes of the endogenous amino acid pools and, may not Journal of Amino Acids reliably re ect the magnitude of the release. e release of preloaded radioactively labeled amino acids from cerebral cortical preparations has been relatively frequently investigated, whereas relatively few studies have been made with the cerebellum [13,14,15]

Summary

Introduction

Glutamate and γγ-aminobutyrate (GABA) are the two major amino acid transmitters in the cerebral cortex and cerebellum, glutamate being responsible for excitatory and GABA for inhibitory transmission [1] In these higher brain regions glycine was earlier assumed to be only an obligatory cotransmitter in the excitatory N-methyl-D-aspartate- (NMDA-) sensitive glutamate receptors, but more recent studies have demonstrated the existence and function of strychninesensitive inhibitory glycine receptors in these structures [2, 3]. In addition to these established neurotransmitters, taurine affects neuronal activity as an inhibitory modulator [4]. We compared the release rates of endogenous GABA, glutamate, aspartate, glycine, and taurine from cerebral cortical and cerebellar slices to estimate the release on a molar basis under normoxic and ischemic conditions. e cerebral cortex and cerebellum represent functionally different brain structures, the cerebellum being predominantly inhibitory and the cerebral cortex with mixed functions, including excitation

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