Seizures decrease regional enzymatic hydrolysis of N-acetyl-aspartylglutamate in rat brain.
Previous results have shown that kindled seizures increase N-acetyl-aspartylglutamate (NAAG) levels in the entorhinal cortex, while non-kindled convulsions have no effect. To further explore possible relationships between epilepsy and the physiology of NAAG, the effect of amygdaloid kindling on the activity of a NAAG-hydrolyzing enzyme was examined in specific brain regions associated with limbic seizures. NAAG is hydrolyzed into glutamate (Glu) and N-acetyl-aspartate (NAA) by N-acetylated-alpha-linked acidic dipeptidase (NAALADase), a membrane-bound peptidase. We found that convulsions decreased NAALADase activity and these effects were generalized to several brain regions. While small decreases in the hippocampus were specific to kindling, the decreases in other limbic regions were larger, non-specific, and appear to be aftereffects of convulsions; i.e. not specific to kindling. Although there is evidence that NAAG may be an excitatory neurotransmitter, it could also function as a storage form of Glu. Thus, a reduction in NAALADase activity could reduce the availability of Glu at certain synapses, which might be a homeostatic mechanism for lessening susceptibility to further seizures.
Meyerhoff
J L
JL
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307.
Robinson
M B
MB
Bixler
M A
MA
Richards
S S
SS
Coyle
J T
JT
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004150:Dipeptidases / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism*; D043425:Glutamate Carboxypeptidase II; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000378:metabolism*
D004151:Dipeptides; C027172:isospaglumic acid; D004150:Dipeptidases; D043425:Glutamate Carboxypeptidase II