Exp Mol Med.  2005 Dec;37(6):533-545.

Role of gamma-aminobutyric acid B (GABA B) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus

Affiliations
  • 1Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea. hwsuh@hallym.ac.kr

Abstract

Kainic acid (KA) is well-known as an excitatory, neurotoxic substance. In mice, KA administered intracerebroventricularly (i.c.v.) lead to morphological damage of hippocampus expecially concentrated on the CA3 pyramidal neurons. In the present study, the possible role of gamma-aminobutyric acid B (GABA B) receptors in hippocampal cell death induced by KA (0.1 microgram) administered i.c.v. was examined. 5-Aminovaleric acid (5-AV; GABA B receptors antagonist, 20 microgram) reduced KA-induced CA3 pyramidal cell death. KA increased the phosphorylated extracellular signal-regulated kinase (p-ERK) and Ca2+ /calmodulin-dependent protein kinase II (p-CaMK II) immunoreactivities (IRs) 30 min after KA treatment, and c-Fos, c-Jun IR 2 h, and glial fibrillary acidic protein (GFAP), complement receptor type 3 (OX-42) IR 1 day in hippocampal area in KA-injected mice. 5-AV attenuated KA-induced p-CaMK II, GFAP and OX-42 IR in the hippocampal CA3 region. These results suggest that p-CaMK II may play as an important regulator on hippocampal cell death induced by KA administered i.c.v. in mice. Activated astrocytes, which was presented by GFAP IR, and activated microglia, which was presented by the OX-42 IR, may be a good indicator for measuring the cell death in hippocampal regions by KA excitotoxicity. Furthermore, it showed that GABA B receptors appear to be involved in hippocampal CA3 pyramidal cell death induced by KA administered i.c.v. in mice.

Keyword

gamma-aminobutyric acid; 5-aminovaleric acid; astrocytes; GABA; hippocampus; kainic acid; microglia; receptors

MeSH Terms

Amino Acids, Neutral/pharmacology
Animals
Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism
Cell Death/drug effects
Extracellular Signal-Regulated MAP Kinases/metabolism
Glial Fibrillary Acidic Protein/metabolism
Hippocampus/anatomy & histology/*cytology/*drug effects
Kainic Acid/*toxicity
Mice
Mice, Inbred ICR
Mossy Fibers, Hippocampal/drug effects/metabolism
Phosphorylation/drug effects
Proto-Oncogene Proteins c-fos/metabolism
Proto-Oncogene Proteins c-jun/metabolism
Receptors, GABA-B/*metabolism
Research Support, Non-U.S. Gov't
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