Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.
Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity.
Matsu-ura
Toru
T
Department of Biology, Faculty of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Konishi
Yoshiyuki
Y
Aoki
Tsutomu
T
Naranjo
Jose R
JR
Mikoshiba
Katsuhiko
K
Tamura
Taka-aki
TA
D000818:Animals; D002135:Calcium-Binding Proteins; D003292:Convulsants / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017403:In Situ Hybridization; D007608:Kainic Acid / Q000494:pharmacology; D051605:Kv Channel-Interacting Proteins; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors
D002135:Calcium-Binding Proteins; D003292:Convulsants; C496756:Csen protein, mouse; D051605:Kv Channel-Interacting Proteins; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D012097:Repressor Proteins; D016291:Dizocilpine Maleate; D003513:Cycloheximide; D007608:Kainic Acid; D010433:Pentylenetetrazole