Uridine release during aminopyridine-induced epilepsy.
Uridine, like adenosine, is released under sustained depolarization and it can inhibit hippocampal neuronal activity, suggesting that uridine may be released during seizures and can be involved in epileptic mechanisms. In an in vivo microdialysis study, we measured the extracellular changes of nucleoside and amino acid levels and recorded cortical EEG during 3-aminopyridine-induced epilepsy. Applying silver impregnation and immunohistochemistry, we examined the degree of hippocampal cell loss. We found that extracellular concentration of uridine, adenosine, inosine, and glutamate increased significantly, while glutamine level decreased during seizures. The release of uridine correlated with seizure activity. Systemic and local uridine application was ineffective. The number of parvalbumin- and calretinin-containing interneurons of dorsal hippocampi decreased. We conclude that uridine is released during epileptic activity, and suggest that as a neuromodulator, uridine may contribute to epilepsy-related neuronal activity changes, but uridine analogues having slower turnover would be needed for further investigation of physiological role of uridine.
Slézia
A
A
Research Group of Neurobiology of the Hungarian Academy of Sciences, Eötvös Loránd University, H-1117 Budapest, Hungary.
Kékesi
A K
AK
Szikra
T
T
Papp
A M
AM
Nagy
K
K
Szente
M
M
Maglóczky
Zs
Z
Freund
T F
TF
Juhász
G
G
D000596:Amino Acids / Q000378:metabolism; D000631:Aminopyridines; D000818:Animals; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis; D009705:Nucleosides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014529:Uridine / Q000378:metabolism* / Q000494:pharmacology*
D000596:Amino Acids; D000631:Aminopyridines; D009705:Nucleosides; C031283:3-aminopyridine; D014529:Uridine