Hippocampal granule cells express glutamic acid decarboxylase-67 after limbic seizures in the rat.
Temporal lobe epilepsy is the most common form of epilepsy. Decreased GABA-ergic inhibition has been suggested as one cause of hyperexcitability. On the other hand, increased expression of glutamic acid decarboxylase, the rate-limiting enzyme of GABA synthesis, has been found in interneurons of the hippocampus in patients with temporal lobe epilepsy and in rats after kainic acid-induced limbic seizures, indicating increased GABA-ergic transmission. Here we report differential expression of two genes encoding different molecular forms of glutamic acid decarboxylase (GAD), GAD65 and GAD67, after kainic acid-induced seizures in the rat. There is a rapid but transient elevation of GAD67 mRNA levels in granule cells 6-24 h after kainic acid injection, followed by enhanced GAD immunoreactivity in the terminal field of mossy fibers. In interneurons in the hilus of the dentate gyrus, a sustained and progressing increase in the expression of both GAD65 and GAD67 messenger RNA occurs. These observations indicate that consitutively glutamatergic mossy fibers may be capable of synthetizing and utilizing the inhibitory transmitter GABA in sustained limbic seizures. Enhanced expression of glutamic acid decarboxylases within interneurons and in granule cells/mossy fibers suggest augmented GABA-ergic neurotransmission supporting selfprotective, anticonvulsive mechanisms in limbic epilepsy.
Schwarzer
C
C
Department of Pharmacology, University of Innsbruck, Austria.
Sperk
G
G
D000818:Animals; D001483:Base Sequence; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008032:Limbic System / Q000503:physiopathology*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000378:metabolism* / Q000503:physiopathology
D012333:RNA, Messenger; D005968:Glutamate Decarboxylase