CELL-SIZE AND THE HEAT-SHOCK RESPONSE IN RAT-BRAIN

The expression of mRNAs encoding two members of the heat-shock protein 70 family, the constitutively-expressed heat-shock cognate (hsc70) mR NA and the strictly heat-inducible (hsp70) mRNA, was quantitated in ce rebellar and hippocampal cells of rats 3 h after amphetamine-induced o r heat-induced hyperthermia. Intracellular heat-shock mRNA levels in s pecific cell types were compared with those of total polyadenylic acid [poly(A)] mRNA or 18S rRNA in the same cell type. Levels of poly(A) m RNAs, 18S rRNAs, and hsc70 mRNAs were highest in large neurons and low est in glia. hsp70 mRNAs were also present at highest levels in large neurons, suggesting that hsp70 mRNAs accumulated as rapidly in these c ell types as they did in small neurons and glia. However, compared wit h levels of intracellular poly(A) mRNAs or levels of rRNAs, large neur ons contained two-to 12-fold lower levels of hsp70 mRNAs than neurons of intermediate size and five- to 30-fold lower levels than glia. Thes e results suggest that hsp70 mRNAs accumulated as rapidly in large neu rons as in small neurons and glia, but that the large size of these ne urons precluded intracellular hsp70 mRNA concentrations increasing as quickly. The susceptibility of large neurons to stress-induced cell de ath could be due, in part, to their inability to synthesize rapidly hs p70 in sufficient amounts to protect these cells from the initial mole cular consequences of stress.