Glutamatergic alterations in the cortex of genetic absence epilepsy rats.
BACKGROUND
In absence epilepsy, the neuronal hyper-excitation and hyper-synchronization, which induce spike and wave discharges in a cortico-thalamic loop are suspected to be due to an imbalance between GABA and glutamate (GLU) neurotransmission. In order to elucidate the role played by GLU in disease outcome, we measured cortical and thalamic extracellular levels of GLU and GABA. We used an in vivo quantitative microdialysis approach (no-net-flux method) in an animal model of absence epilepsy (GAERS). In addition, by infusing labelled glutamate through the microdialysis probe, we studied in vivo glutamate uptake in the cortex and thalamus in GAERS and non-epileptic control (NEC) rats. Expression of the vesicular glutamate transporters VGLUT1 and VGLUT2 and a synaptic component, synaptophysin, was also measured.


RESULTS
Although extracellular concentrations of GABA and GLU in the cortex and thalamus were not significantly different between GAERS and NEC rats, cortical GLU uptake was significantly decreased in unrestrained awake GAERS. Expression of VGLUT2 and synaptophysin was increased in the cortex of GAERS compared to NEC rats, but no changes were observed in the thalamus.


CONCLUSIONS
The specific decrease in GLU uptake in the cortex of GAERS linked to synaptic changes suggests impairment of the glutamatergic terminal network. These data support the idea that a change in glutamatergic neurotransmission in the cortex could contribute to hyperexcitability in absence epilepsy.
Touret
Monique
M
INSERM, U842, Lyon; Université de Lyon, Lyon1, Faculté de Médecine Laennec, UMR-S842, Lyon, F-69372, France. touret@univ-lyon1.fr
Parrot
Sandrine
S
Denoroy
Luc
L
Belin
Marie-Françoise
MF
Didier-Bazes
Marianne
M
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004832:Epilepsy, Absence / Q000235:genetics* / Q000378:metabolism*; D018698:Glutamic Acid / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D050496:Vesicular Glutamate Transport Proteins / Q000096:biosynthesis / Q000235:genetics
D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid