NEURONAL INDUCTION OF 72-KDA HEAT-SHOCK PROTEIN FOLLOWING METHAMPHETAMINE-INDUCED HYPERTHERMIA IN THE MOUSE HIPPOCAMPUS

By means of an immunohistochemical technique, we examined the neuronal induction of 72-kDa heat shock protein (HSP72) in response to methamp hetamine-induced hyperthermia in the mouse hippocampus. Strong HSP72 i mmunoreactivity (ir) was found in the neurons of hippocampus proper, p articularly in the CA1/2 and medial CA3 subfields, at 10 h after drug injection. By 18 h, those neurons still revealed HSP72-ir, while neuro ns of the dentate gyrus also appeared positive for HSP72. At this stag e, intense HSP72-ir was first detected in non-neuronal cells, i.e. gli al and vascular endothelial cells. At 24 h, no apparent HSP72-ir was f ound in the hippocampal neurons, while only non-neuronal cells still r evealed immunoreactivity for HSP72. In addition, no morphological evid ence of cell degeneration or loss was noted in the CA1 sector or other hippocampal regions at 5 days after hyperthermic insult. In conclusio n, (1) methamphetamine-induced hyperthermia per se is a stressful stim ulant causing neuronal induction of HSP72 in the hippocampus neurons, particularly of CA1/2 and medial CA3 sectors, but does not prove fatal to the cells; (2) there is a cell type-specific difference in respons e to hyperthermic insult by inducing HSP72 and the timing of the induc tion response in the hippocampal formation; and (3) the animals that u nderwent drug-induced hyperthermia may be useful as an experimental mo del for the study of the protective mechanism of heat shock proteins a gainst subsequent harmful stimuli.