Neuronal hyperexcitability and seizures are associated with changes in glial-neuronal interactions in the hippocampus of a mouse model of epilepsy with mental retardation.
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 vivo(13) C magnetic resonance spectroscopy, after simultaneous injection of [1-(13) C]glucose and [1,2-(13) C]acetate, followed by decapitation, showed decreased [1,2-(13) C]GABA formation from hippocampal astrocytic precursors and a marked reduction in [4,5-(13) C]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.
Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Torun
T
Melø
Paolo
P
Bigini
Ursula
U
Sonnewald
Silvia
S
Balosso
Alfredo
A
Cagnotto
Sara
S
Barbera
Sarah
S
Uboldi
Annamaria
A
Vezzani
Tiziana
T
Mennini
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008607:Intellectual Disability / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D012640:Seizures / Q000150:complications / Q000378:metabolism / Q000473:pathology*