Neuronal hyperexcitability and seizures are associated with changes in glial-neuronal interactions in the hippocampus of a mouse model of epilepsy with mental retardation

作者：Melo Torun; Bigini Paolo; Sonnewald Ursula; Balosso Silvia; Cagnotto Alfredo; Barbera Sara; Uboldi Sarah; Vezzani Annamaria; Mennini Tiziana^*

来源：Journal of Neurochemistry, 2010, 115(6): 1445-1454.

DOI：10.1111/j.1471-4159.2010.07048.x

• 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.

• 出版日期2010-12