Rearing environment, sex and developmental lead exposure modify gene expression in the hippocampus of behaviorally naïve animals

Developmental lead (Pb) exposure impairs various cognitive processes and behaviors in both humans and animals. In particular, specific deficits in spatial learning and memory have been described in Pb-exposed rats. It is also known that rearing environment (i.e., non-enriched vs. enriched) can have significant influences on cognitive performance and that rearing environment and sex may modify the influence of Pb exposure on learning and memory processes. It is also known that behavioral testing can alter hippocampal gene expression and interactive effects of environment. Little is known however about the molecular correlates of developmental Pb-exposure on expression of key sets of cognition-relevant genes in the hippocampus and how sex and environmental rearing condition may modify these effects. The present study examined expression profiles of neurobiologically-relevant genes (i.e., neurotrophic factors, NMDA receptors, metabotropic glutamate receptors, synaptic function/plasticity, and transcription/gene regulation) in behaviorally naïve rats with perinatal exposure (i.e., gestation through weaning) to different levels of Pb (250, 750 and 1500 ppm Pb acetate) in males and females raised in a non-enriched environment (standard housing without toys) or an enriched environment (large cage containing toys changed twice weekly). Unlike previous studies identifying gene changes following behavioral testing, which alters expression analysis, we identified both sex and environmental related changes in hippocampal genes following Pb exposure alone. The gene expression changes described may be associated with learning and memory and may pre-determine how cognitive profiles develop following Pb exposure.

► Sex alone modifies hippocampal gene expression following lead exposure.
► Environmental enrichment modifies hippocampal gene expression after lead exposure.
► Lead exposure may pre-determine cognitive profiles through hippocampal gene expression.