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 characte rize the mRNA expression of a-tubulin, a neuroprotein crucial for neur onal structural and functional restoration. in comparison to that of t he stress inducible heat shock protein-70 (HSP-70), in the same gerbil brain following 10 min of forebrain ischemia. The HSP-70 expression w as 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 t he other hand, was expressed in all pyramidal fields of the hippocampu s as well as dentate gyrus in nonischemic controls. A decline was note d in the CA1 region 1 h PI onward and was maximal at 6 h PI. Its expre ssion, however, increased at 24 h PI (significant only in comparison t o 15 min and 6 h PI but not to control) when it became rather strong i n the dentate gyrus. Thus, the temporal pattern of expression of a-tub ulin sharply contrasted with that of HSP-70 in the PI brain as it decl ined in the vulnerable CA1 region during the 1st 24 h PI, i.e., the pe riod 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 ische mia, 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 co rrelation between the loss of alpha-tubulin mRNA and delayed neuronal necrosis that follows in the vulnerable CA1 region.