期刊
JOURNAL OF NEUROCHEMISTRY
卷 115, 期 6, 页码 1445-1454出版社
WILEY
DOI: 10.1111/j.1471-4159.2010.07048.x
关键词
13C nuclear magnetic resonance spectroscopy; astrocytes and microglia; glutamate and GABA; hippocampus; neuronal ceroid lipofuscinosis; seizures
P>Hippocampal excitability and the metabolic glial-neuronal interactions were investigated in 22-week-old mice with motor neuron degeneration (mnd), a model of progressive epilepsy with mental retardation. Mnd mice developed spontaneous spikes in the hippocampus and were more susceptible to kainate-induced seizures compared with control mice. Neuronal hyperexcitability in their hippocampus was confirmed by the selective increase of c-Fos positive nuclei. Glial activation and pro-inflammatory cytokines over-expression were observed in the hippocampus of mnd mice, even in the absence of marked hippocampal neurodegeneration, as suggested by unchanged amounts of neuroactive amino acids and N-acetyl aspartate. Concentration of other amino acids, including GABA and glutamate, was not changed as well. However, ex vivo13C magnetic resonance spectroscopy, after simultaneous injection of [1-13C]glucose and [1,2-13C]acetate, followed by decapitation, showed decreased [1,2-13C]GABA formation from hippocampal astrocytic precursors and a marked reduction in [4,5-13C]glutamate derived from glutamine. We suggest that astrocyte dysfunction plays a primary role in the pathology and that mnd mice are of value to investigate early pathogenetic mechanism of progressive epilepsy with mental retardation.
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