The molecular signature of anxiety-like behaviour in mice exposed to a postnatal immune challenge

Abstract

The development of stress-reactivity and emotionality has been shown by both clinical and preclinical work to be influenced by the early immune environment.  Immune challenge with lipopolysaccharide (LPS) during the first postnatal week in rodents leads to long-term alterations in anxiety-like behaviour. Given that indicators of anxiety often present during adolescence in the clinical population, our work focused on identifying molecular alterations across development that may contribute to the early emergence of anxiety.  In particular we examined neuroplasticity-related substrates, including BDNF and serotonergic gene expression, as well as hippocampal neurogenesis. Mice were administered LPS (0.05mg/kg, i.p.) on postnatal days 3 and 5.  Gene expression was examined in parallel with assessment of exploratory and anxiety-like behaviours during development.  Adult hippocampal neurogenesis was assessed by immunoreactivity for BrdU and doublecortin.  Molecular analysis revealed an altered spatiotemporal profile of BDNF and serotonergic gene expression in LPS-mice during the developmental time period in which anxiety emerges.  This was concurrent with reduced exploratory behaviour in male LPS-mice and increased anxiety-like behaviour in female LPS-mice; both of which persisted into adulthood.  Female LPS-mice also exhibited altered adult hippocampal neurogenesis which may be linked to this anxiety-like phenotype.  The present study reveals nuances in the developmental nature of anxiety and suggests that altered neuroplasticity-related gene expression and hippocampal neurogenesis may contribute to anxiety-like behaviours.  Elucidating the molecular substrates contributing to anxiety provides insight into the differing susceptibility of the developing CNS to early immune challenge and the possible contribution of these alterations to behavioural dysfunction.