COMPARISON OF ALPHA-TUBULIN MESSENGER-RNA AND HEAT-SHOCK PROTEIN-70 MESSENGER-RNA IN GERBIL BRAIN FOLLOWING 10 MIN OF ISCHEMIA

In situ hybridization and Northern blot analysis were used to characterize the mRNA expression of a-tubulin, a neuroprotein crucial for neuronal structural and functional restoration. in comparison to that of the stress inducible heat shock protein-70 (HSP-70), in the same gerbil brain following 10 min of forebrain ischemia. The HSP-70 expression was noted in the dentate granule layer 1 h postischemia (PI) and became prominent in all pyramidal cell fields of the hippocampus in addition to the dentate layer at 6 h PI, The induction of HSP-70 persisted in CA1 and CA2 regions and partly in dentate gyrus for up to the 1 day PI period examined.There was no significant HSP-70 expression in any of the regions of the nonischemic or 15 min PI brain. Alpha-Tubulin. on the other hand, was expressed in all pyramidal fields of the hippocampus as well as dentate gyrus in nonischemic controls. A decline was noted in the CA1 region 1 h PI onward and was maximal at 6 h PI. Its expression, however, increased at 24 h PI (significant only in comparison to 15 min and 6 h PI but not to control) when it became rather strong in the dentate gyrus. Thus, the temporal pattern of expression of a-tubulin sharply contrasted with that of HSP-70 in the PI brain as it declined in the vulnerable CA1 region during the 1st 24 h PI, i.e., the period when HSP-70 was induced and its expression was lowest in the 6 h group when HSP-70 peaked. It was maximum in the dentate gyrus at 24 h PI when HSP-70 was marginally detectable in that region. These studies indicate that in early recirculation period following prolonged ischemia, HSP-70 mRNA is expressed in both vulnerable regions as well as in regions of the brain that are destined to survive while alpha-tubulin is diminished in vulnerable regions. These data suggest a positive correlation between the loss of alpha-tubulin mRNA and delayed neuronal necrosis that follows in the vulnerable CA1 region.