Abstract Body

Early-life stress (ELS) can lastingly impair cognitive functioning and alter the neuroimmune profile. Recently, we showed that an early dietary intervention with a low omega (ω)-6/ω-3 ratio protects against both ELS-induced cognitive deficits and increased phagocytic microglia inadulthood. To gain further insight into how early-life ω-3 availability affects the (neuro-)immune system, and to what extent this might contribute to its beneficial effects on cognition, we here tested how ELS and early dietary ω-6/ω-3 ratio affects the response to an acute immune challenge in adulthood.

Mice were exposed to chronic ELS by limiting nesting material from postnatal(P)2 to P9, and provided with a diet containing a high or low ω-6/ω-3 ratio from P2 to P42. At P120, cognitive functioning was assessed using the object location task. Subsequently, a single lipopolysaccharide (LPS) injection was given. After 24 hours, peripheral cytokine levels and hippocampal genome-wide gene expression were measured using multiplex and microarray respectively.

An early diet with a low ω-6/ω-3 ratio prevented ELS-induced cognitive deficits. LPS increased plasma cytokine levels with a subtle modulation by ELS but no effect of early diet. Interestingly, while ELS and diet barely affected global hippocampal gene expression under baseline conditions, the effects of ELS and diet were unmasked when studied in response to LPS. Our data indicate that short-term exposure to stress and an altered dietary ω-6/ω-3 ratio during early-life program the neuroinflammatory response to an immune challenge. This study gives new insights for the development of targeted dietary interventions for vulnerable populations.