Distinct changes in neuronal and astrocytic amino acid neurotransmitter metabolism in mice with reduced numbers of synaptic vesicles

被引:9
作者
Bogen, Inger Lise [1 ]
Risa, Oystein [2 ]
Haug, Kristin H. [1 ]
Sonnewald, Ursula [2 ]
Fonnum, Frode [1 ]
Walaas, S. Ivar [1 ]
机构
[1] Univ Oslo, Inst Basic Med Sci, Fac Med, Dept Biochem, N-0317 Oslo, Norway
[2] Norwegian Univ Sci & Technol, Fac Med, Dept Neurosci, N-7034 Trondheim, Norway
关键词
GABA; glutamate; neurotransmitter metabolism; NMR; synapsin; synaptic vesicles;
D O I
10.1111/j.1471-4159.2008.05344.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The relations between glutamate and GABA concentrations and synaptic vesicle density in nerve terminals were examined in an animal model with 40-50% reduction in synaptic vesicle numbers caused by inactivation of the genes encoding synapsin I and II. Concentrations and synthesis of amino acids were measured in extracts from cerebrum and a crude synaptosomal fraction by HPLC and (13)C nuclear magnetic resonance spectroscopy (NMRS), respectively. Analysis of cerebrum extracts, comprising both neurotransmitter and metabolic pools, showed decreased concentration of GABA, increased concentration of glutamine and unchanged concentration of glutamate in synapsin I and II double knockout (DKO) mice. In contrast, both glutamate and GABA concentrations were decreased in crude synaptosomes isolated from synapsin DKO mice, suggesting that the large metabolic pool of glutamate in the cerebral extracts may overshadow minor changes in the transmitter pool. (13)C NMRS studies showed that the changes in amino acid concentrations in the synapsin DKO mice were caused by decreased synthesis of GABA (20-24%) in cerebral neurons and increased synthesis of glutamine (36%) in astrocytes. In a crude synaptosomal fraction, the glutamate synthesis was reduced (24%), but this reduction could not be detected in cerebrum extracts. We suggest that lack of synaptic vesicles causes down-regulation of neuronal GABA and glutamate synthesis, with a concomitant increase in astrocytic synthesis of glutamine, in order to maintain normal neurotransmitter concentrations in the nerve terminal cytosol.
引用
收藏
页码:2524 / 2534
页数:11
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