Oja Simo S, Saransaari Pirjo
Department of Paediatrics, Tampere University Hospital, Tampere, Finland.
Neurochem Res. 2009 Sep;34(9):1668-76. doi: 10.1007/s11064-009-9961-4. Epub 2009 Apr 3.
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.
神经递质和调质的释放大多是使用标记的预加载化合物进行研究的。然而,由于多种原因,估计的释放量可能无法可靠地反映内源性化合物的释放情况。现在,在对照和缺血条件下,研究了7日龄和3月龄小鼠海马体和脑干切片中神经活性内源性氨基酸γ-氨基丁酸(GABA)、甘氨酸、牛磺酸、L-谷氨酸和L-天冬氨酸的基础释放和钾离子诱发释放。为作比较,评估了突触非活性的L-谷氨酰胺、L-丙氨酸、L-苏氨酸和L-丝氨酸的释放情况。海马体和脑干的估计值明显不同,在发育中的小鼠和成年小鼠中也有所不同。3月龄小鼠的GABA释放量比7日龄小鼠大得多,而牛磺酸的情况则相反,尤其是在海马体中。钾离子刺激在成熟脑干中比未成熟脑干中更能增强甘氨酸的释放,而在海马体中则观察到相反的情况。缺血增强了两个脑区所有神经活性氨基酸的释放,在3月龄小鼠的海马体中,GABA、天冬氨酸和谷氨酸的影响相对最为明显,在脑干中,7日龄小鼠的牛磺酸和3月龄小鼠的甘氨酸影响相对最为明显。这些结果在定性上与早期使用标记预加载氨基酸进行的实验结果相似。然而,使用放射性标记无法完全正确地估计释放量的大小。在发育中的小鼠中,只有牛磺酸的释放可能会抵消海马体和脑干缺血时兴奋性氨基酸的有害影响。