THE EFFECT OF HYPOXIA AND CATECHOLAMINES ON REGIONAL EXPRESSION OF HEAT-SHOCK PROTEIN-72 MESSENGER-RNA IN NEONATAL PIGLET BRAIN

The present study has shown that hypoxia leads to expression of heat-s hock protein in the brain of newborn piglets and this process is almos t completely abolished by depletion of catecholamines prior to the hyp oxic episode. The piglets were anesthetized and mechanically ventilate d. One hour of hypoxia was generated by decreasing the oxygen fraction in the inspired gas (FiO2) from 22% to 6%-10%. FiO2 was then returned to the control value for a period of 2 h. Following the 2 h of reoxyg enation, regional expression of the 72-kDa heat-shock protein (hsp72) mRNA was determined using in situ hybridization and autoradiography. T he hypoxic insult (cortical pO(2) = 3-10 mmHg) induced expression of h sp72 mRNA in regions of both white and gray matter, with strong expres sion occurring in the cerebral cortex of individual animals. Depleting the brain of catecholamines prior to hypoxia, by treating the animals with alpha-methyl-p-tyrosine (AMT), resulted in a major change in the hsp72 mRNA expression. In the catecholamine depleted group of animals , the intensity of hsp72 mRNA expression was greatly decreased or almo st completely abolished relative to the nondepleted hypoxic group. The se results suggest that the catecholamines play a significant role in the expression of the hsp72 gene in response to hypoxic insult in neon atal brain.