Changes in Caspase-3 Activity in Early Ontogenesis Lead to Impairments to Memory and Learning in Adult Rats

Abstract

We report here the first observations of time-delayed degradation of the ability to learn and remember in rats after changes in the level of caspase-3 activity in early postnatal ontogeny. Administration of intracerebroventricular caspase inhibitor Ac-DEVD-CHO to 20-day-old rat pups was followed by impairments to memory and learning, along with anomalous increases in caspase-3 activity on post-treatment day 7; impairments were also present 30–45 days after treatment, when the activity level of this enzyme was normal for age. An analogous picture was seen in young and adult rats after prenatal hypoxia (7% O2, 3 h, on E14). In addition, the stronger and longer-lasting increases in caspase-3 activity seen after prenatal hypoxia were found to be accompanied by more significant impairments to memory and learning on testing in a two-level radial maze. The positive correlation found between the magnitude of changes in caspase activity in early ontogeny and impairments to cognitive functions in adults points to the need to maintain optimum caspase-3 activity at the early stage of development to support the normal formation of the brain and behavior during maturation. The fact that these cognitive impairments occurring in conditions of altered caspase-3 in the first month of postnatal development were seen regardless whether or not intense cell death occurred supports the hypothesis that this enzyme has an important nonapoptotic function in early ontogeny.