The effect of early life immune challenge on adult forced swim test performance and hippocampal neurogenesis

Abstract

Many psychiatric diseases can be considered neurodevelopmental in nature and accumulating evidence links immune system dysfunction to disease etiology. Yet, it is currently unknown how the immune system alters brain function through development to increase susceptibility to psychiatric illness. Neonatal immune challenge in rodents is a neurodevelopmental model that has been associated with long-term molecular and behavioural changes in stress-reactivity. As enhanced stress-reactivity is associated with the emergence of depressive-like behaviours concurrent with hippocampal pathology, we measured depressive-like behaviour in the forced swim test and hippocampal neurogenesis in adult mice neonatally exposed to lipopolysaccharide LPS; 0.05 mg/kg, i.p. on postnatal days 3 and 5. As there are important functional differences along the ventral-dorsal hippocampus axis, ventral and dorsal hippocampal neurogenesis were measured separately. Our findings reveal a sexually-dimorphic response to early-life LPS challenge. Male LPS-mice spent less time immobile in the forced swim test, suggesting altered reactivity to swim stress. This was accompanied by an increase in doublecortin-positive cells in the dorsal hippocampus of female mice. These findings demonstrate that exposure to an immune challenge during critical developmental time periods leads to long-term sexually-dimorphic alterations in stress-reactivity that are accompanied by changes to adult hippocampal neurogenesis.