The Involvement of Heat Shock Protein in the Delayed Neuronal Death of the Mongolian Gerbil Hippocampal Pyramidal Neurons.

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Although apoptosis is most likely the main cause of delayed neuronal death (DND) in the hippocampal pyramidal neurons after transient ischemia, the molecular mechanisms underlying this phenomenon have not been elucidated clearly. Recently Heat Shock Protein 90 (HSP90) attracts attention as one of protective factor for stress, but the details of its function are scarsely elucidated.Male Mongolian gerbils (n=), weighing 60 to 70 g, were anesthetized with isoflurane. Transient forebrain ischemia was induced by occluding the bilateral common carotid arteries for 5 minutes. A sham-operation group was not subjected to ischemia and served as the negative control. The animals were sacrificed 6-120 hours after ischemia and the hippocampi were dissected. We analyzed expression and localization of HSP90 using RT-PCR, Western blot analysis, and immunohistochemistry. In addition, HSP90 was induced by geranylgeranyl acetone and the function of HSP90 was examined.RT-PCR and Western blot analysis showed that HSP90 mRNA was up-regulated at 6 to 48 hours and HSP90 was increased at 12 to 48 hours after ischemia in the pyramidal neurons. While an increase in HSP90 was also verified by immunohistochemistry in the hippocampus after ischemia, the expression was weak in the CAI region compared to that in CA2. Intraperitoneal administration of geranylgeranylacetone, 400 mg/kg, 4 hours before ischemia induced expression of HSP90 at 48 hours after ischemia and ameliorated DNA fragmentation and DND at 96 hours after ischemia in the pyramidal neurons.These results strongly indicate that HSP90 is protective against DND after transient ischemia in the Mongolian Gerbil. In addition, difference in the ability of HSP90 induction may be involved in selective neuronal vulnerability.