The effect of dizocilpine and enadoline on immediate early gene expression in the gerbil global ischaemia model.
Increases in mRNA levels for c-fos, c-jun, junB, hsp70 and NGFI-A were observed in the dentate gyrus of the hippocampus following 7 min ischaemia in the Mongolian gerbil. The response was rapid and transient (30 min to 4 hr) for NGFI-A, junB and c-fos mRNA. In contrast c-jun mRNA remained increased for several hours. Hsp70 increased in the dentate gyrus 1 hr after the insult, returned to control values at 4 hr and showed a secondary increase at 24 hr. At 24 hr increased hsp70 mRNA was observed in other regions of the CNS, i.e. CA1, CA2, CA3 and cortex. The non-competitive NMDA receptor antagonist, dizocilpine, attenuated the increases in IEG expression and was neuroprotective. In contrast the kappa opiate receptor agonist, enadoline, protected the CA1 neurones from degeneration but did not inhibit the increased levels of IEG mRNA. Increases in hsp70 mRNA were reduced to baseline by both enadoline and dizocilpine. These results suggest that inhibition of IEG expression is not a prerequisite for neuroprotection. However, hsp70 was predictive of neuronal protection and may be a useful assay in this and related models.
Woodburn
V L
VL
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, U.K.
Hayward
N J
NJ
Poat
J A
JA
Woodruff
G N
GN
Hughes
J
J
D000818:Animals; D001345:Autoradiography; D001572:Benzofurans / Q000494:pharmacology*; D002545:Brain Ischemia / Q000378:metabolism*; D004268:DNA-Binding Proteins; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D005849:Gerbillinae; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D014157:Transcription Factors
D001572:Benzofurans; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D011759:Pyrrolidines; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D014157:Transcription Factors; D016291:Dizocilpine Maleate; C067110:enadoline