KAINIC ACID-INDUCED HEAT-SHOCK PROTEIN-70, MESSENGER-RNA AND PROTEIN EXPRESSION IS INHIBITED BY MK-801 IN CERTAIN RAT-BRAIN REGIONS

The regional expression of inducible 72 kDa heat shock protein (HSP-70 ), HSP-70 mRNA and the neuropathological outcome of their expression w ere examined in the rat brain following systemic administration of kai nic acid (9 mg/kg), and also after pretreatment with the non-competiti ve N-methyl-D-aspartate antagonist MK-801 (1 mg/kg). Five hours after administration of kainic acid alone, dense expression of HSP-70 mRNA w as found within the limbic system, mainly in the hippocampus, piriform and entorhinal cortices, amygdaloid complex, thalamic nuclei, subicul um and in other cortical areas in rats that had shown convulsive behav iour. At 24 h, HSP-70 immunoreactivity was seen in most areas previous ly expressing HSP-70 mRNA, except the piriform and entorhinal cortices and several ventral nuclei of the amygdaloid complex. Histopathologic al examination at 24 h revealed marked cell loss in these latter regio ns and less severe histopathological changes in other areas of the lim bic system in brains of convulsive rats. No alterations were apparent in non-convulsive rats. The percentage of rats showing convulsive beha viour with kainic acid was reduced from 74 to 4% following pretreatmen t with MK-801. In addition, MK-801 inhibited the kainic acid-induced e xpression of HSP-70 mRNA and protein in certain brain regions, notably the cortex, the pyramidal cell layer of CA1, and discrete thalamic nu clei, However, HSP-70 mRNA induction was sustained in the pyramidal ce ll layer of CA3, the amygdaloid complex and the subiculum, despite the fact that none of these rats convulsed. MK-801 prevented necrosis in all rats examined except the single rat that had shown convulsive beha viour. These results show that early regional expression of inducible HSP-70 mRNA allows the visualization of regions affected by kainic aci d and maps regions inhibited by MK-801. In addition, the results ident ify brain regions putatively involved in the manifestation of limbic c onvulsions. Furthermore, these data illustrate that the induction of H SP-70 mRNA is not predictive of cell death or survival.