Gene profiling the response to kainic acid induced seizures.
Kainic acid activates non-N-methyl-d-aspartate (NMDA) glutamate receptors where it increases synaptic activity resulting in seizures, neurodegeneration, and remodeling. We performed microarray analysis on rat hippocampal tissue following kainic acid treatment in order to study the signaling mechanisms underlying these diverse processes in an attempt to increase our current understanding of mechanisms contributing to such fundamental processes as neuronal protection and neuronal plasticity. The kainic acid-treated rats used in our array experiments demonstrated severe seizure behavior that was also accompanied by neuronal degeneration which is suggested by fluoro-jade B staining and anti-caspase-3 immunohistochemistry. The gene profile revealed 36 novel kainic acid regulated genes along with additional genes previously reported. The functional roles of these novel genes are discussed. These genes mainly have roles in transcription and to a lesser extent have roles in cell death, extracellular matrix remodeling, cell cycle progression, neuroprotection, angiogenesis, and synaptic signaling. Gene regulation was confirmed via quantitative real time polymerase chain reaction and in situ hybridization.
Hunsberger
Joshua G
JG
Yale University School of Medicine, 34 Park Street, CMHC, New Haven, CT 06520, USA.
Bennett
Alica H
AH
Selvanayagam
Emmanuel
E
Duman
Ronald S
RS
Newton
Samuel S
SS
D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005109:Extracellular Matrix / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000473:pathology / Q000502:physiology; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000235:genetics
D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D007608:Kainic Acid