Regulation of caspase-3 content and activity in rat cortex in norm and after prenatal hypoxia

Abstract

The analysis of caspase-3 activity, content and regulation in the brain cortex during the first month of postnatal ontogenesis in rats with normal development and after prenatal normobaric hypoxia on ?14 (3 h, 7% O2) has been performed. Prenatal hypoxia compared to controls was found to result in a statistically significant increase in the content (3.6-fold) and activity (5.3-fold) of caspase-3 in the neocortex of rats in the period of the most intensive synaptogenesis and cell elimination (P20–P35). A single intraventricular injection on ?20 of a caspase inhibitor Ac-DEVD-CHO altered the activity and content of this enzyme although the dynamics of the changes was different in rats with normal and pathological embryogenesis. In the first hours after inhibitor administration a decrease in caspase-3 activity was observed in both groups of animals. Later, on days 1–5 after injection, there was further decrease of caspase-3 activity (3.9-fold) in rats subjected to prenatal hypoxia although the enzyme content was not significantly different from the age-matched controls. On the contrary, in rats with normal embryogenesis on days 1–5 after the injection there was a significant (two-fold) increase in the content of active caspase-3 form and its enzyme activity (2.5-fold) although these characteristics returned down to the control values on the 15th day after inhibitor administration. After administration of Ac-DEVD-CHO to adult rats (P90) with normal development there was also caspase-3 inhibition 3 h after the injection, however no further increase in its activity on days 1–5 after injection, similar to those observed in young animals, has been found. The data obtained testify to the difference in the agerelated dynamics and regulation of the active form of caspase-3 in the period of the most intensive brain development of rats with normal embryogenesis and subjected to prenatal hypoxia.