Block of glutamate-glutamine cycle between astrocytes and neurons inhibits epileptiform activity in hippocampus.
Recurrent epileptiform activity occurs spontaneously in cultured CNS neurons and in brain slices in which GABA inhibition has been blocked. We demonstrate here that pharmacological treatments resulting in either the block of glutamine production by astrocytes or the inhibition of glutamine uptake by neurons suppress or markedly decrease the frequency of spontaneous epileptiform discharges both in primary hippocampal cultures and in disinhibited hippocampal slices. These data point to an important role for the neuron-astrocyte metabolic interaction in sustaining episodes of intense rhythmic activity in the CNS, and thereby reveal a new potential target for antiepileptic treatments.
Bacci
Alberto
A
Consiglio Nazionale delle Ricerche Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Medical Pharmacology, 20129 Milano, Italy.
Sancini
Giulio
G
Verderio
Claudia
C
Armano
Simona
S
Pravettoni
Elena
E
Fesce
Riccardo
R
Franceschetti
Silvana
S
Matteoli
Michela
M
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002478:Cells, Cultured; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D005110:Extracellular Space / Q000502:physiology; D005456:Fluorescent Dyes; D016257:Fura-2; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D005973:Glutamine / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology; D018715:Microscopy, Video; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats
D005456:Fluorescent Dyes; D018756:GABA Antagonists; D005973:Glutamine; D018698:Glutamic Acid; D016257:Fura-2