Hyperthermia induces gene expression of heat shock protein 70 and phosphorylation of mitogen activated protein kinases in the rat cerebellum

In-vivo heat-shock induced heat shock factor (HSF) DNA-binding activity and accumulation of heat shock protein (hsp)70 mRNA in newborn and adult rat c erebellum was studied. We identified a high basal level of c-Jun N-terminal kinase (JNK) and p38 MAP kinase phosphorylation in the cerebellum, indepen dently of age. Hyperthermia increased JNK1, decreased JNK2 but did not modi fy JNK3 phosphorylation in the newborn cerebellum, whereas decreased the ph osphorylation of both JNK1 and JNK3 in adult rats. During recovery from hyp erthermia, JNK2 phosphorylation returned to control level in the newborn, J NK1 appeared hyperphosphorylated only in the newborn, and JNK3 in all anima ls. JNK2 never appeared phosphorylated in the adult cerebellum. Hyperthermi a increased p38 MAP kinase phosphorylation in the cerebellum, with differen t trends in newborn and adult rats during recovery. Heat shock increased ex tracellular signal-regulated kinase phosphorylation concomitant to tyrosine kinase receptor activation (epidermal growth factor-receptor in the newbor n and insulin-like growth factor-receptor in the adult cerebellum). The beh avior of stress kinases may underlie a different age-related vulnerability to heat stress of the cerebellum. (C) 2001 Elsevier Science Ireland Ltd. Al l rights reserved.