Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure.

Abstract

A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.

• Authors: J Suzukawa, K Omori, G Okugawa, Y Fujiseki, C W Heizmann, C Inagaki
• Journal: Brain research (Brain Res) Vol. 834 Issue 1-2 Pg. 89-102 (Jul 10 1999) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10407097 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1999 Elsevier Science B.V.

Chemical References

• Convulsants
• Excitatory Amino Acid Antagonists
• Nerve Growth Factors
• Parvalbumins
• Proto-Oncogene Proteins c-fos
• RNA, Messenger
• Ethacrynic Acid

Topics

• Animals
• Convulsants (pharmacology)
• Disease Susceptibility
• Epilepsy (chemically induced, metabolism, pathology, physiopathology)
• Ethacrynic Acid
• Excitatory Amino Acid Antagonists (pharmacology)
• Immunohistochemistry
• Interneurons (metabolism, pathology)
• Male
• Mice
• Nerve Growth Factors (genetics)
• Neural Inhibition (physiology)
• Parvalbumins (metabolism)
• Proto-Oncogene Proteins c-fos (genetics)
• RNA, Messenger (metabolism)
• Time Factors
• Tissue Distribution (physiology)