Artificial rearing inhibits apoptotic cell death through action on pro-apoptotic signaling molecules during brain development: Replacement licking partially reverses these effects

Early life stress associated with being reared without mother, siblings, and nest affects the formation of neuronal networks during rat development. Prior work shows that in comparison to mother-reared male rats, artificial rearing results in elevated numbers of neurons in adulthood and reduced apoptosis during the first postnatal week. Replacement with stroking stimulation, designed to simulate mothers' licking, reversed these effects in most brain areas. The present communication explored the effects of early rearing manipulations on signaling proteins. Male rats were reared until postnatal day 7 either in an artificial-feeding paradigm (AR) or with their mothers (MR). AR animals received different amounts of maternal-like stimulation using a soft paintbrush. Brains were extracted and prepared for molecular assays of 1) apoptosis and 2) pro and anti-apoptotic proteins on day 7 of postnatal life. Results showed that stimulation of the AR pups reversed the effects of artificial rearing on apoptosis in a dose dependent manner; low and very high levels of stimulation were without effect whereas moderate levels of stimulation produced effects on apoptosis similar to effects seen in mother-reared controls. Moreover, this artificial rearing effect and the pattern of reversal with stroking were also found for levels of pro-apoptotic Bax protein, the ratio of Bax/Bcl-2 and levels of activated caspase-3 which we believe mediates programmed cell death.