Inflammation early in life is a vulnerability factor for emotional behavior at adolescence and for lipopolysaccharide-induced spatial memory and neurogenesis alteration at adulthood
J Neuroinflammation. 2014-09-17; 11(1):
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1. J Neuroinflammation. 2014 Sep 17;11:155. doi: 10.1186/s12974-014-0155-x.
Inflammation early in life is a vulnerability factor for emotional behavior at
adolescence and for lipopolysaccharide-induced spatial memory and neurogenesis
alteration at adulthood.
Dinel AL, Joffre C, Trifilieff P, Aubert A, Foury A, Le Ruyet P, Layé S.
BACKGROUND: The postnatal period is a critical time window during which
inflammatory events have significant and enduring effects on the brain, and as a
consequence, induce alterations of emotional behavior and/or cognition later in
life. However, the long-term effect of neonatal inflammation on behavior during
adolescence, a sensitive period for the development of neurodevelopmental
psychiatric disorders, has been little studied. In this study, we examined
whether an early-life inflammatory challenge could alter emotional behaviors and
spatial memory at adolescence and adulthood and whether stress axis activity,
inflammatory response and neurogenesis were affected.
METHODS: Lipopolysaccharide (LPS, 100 μg/kg) was administered to mice on
postnatal day (PND) 14 and cytokine expression was measured in the plasma and in
brain structures 3 hours later. Anxiety-like and depressive-like behavior
(measured in the novelty-suppressed feeding test and the forced swim test,
respectively) and spatial memory (Y-maze test) were measured at adolescence
(PND30) and adulthood (PND90). Hypothalamic-pituitary-adrenal (HPA) axis activity
(plasma corticosterone and glucocorticoid receptors in the hippocampus and
prefrontal cortex) was measured at adulthood. In addition, the impact of a novel
adult LPS challenge (100 μ/kg) was measured on spatial memory (Y-maze test),
neurogenesis (doublecortin-positive cell numbers in the hippocampus) and plasma
RESULTS: First, we show in PND14 pups that a peripheral administration of LPS
induced the expression of pro- and anti-inflammatory cytokines in the plasma and
brain structures that were studied 3 hours after administration. Anxiety-like
behavior was altered in adolescent, but not in adult, mice, whereas
depressive-like behavior was spared at adolescence and increased at adulthood.
This was accompanied by a decreased phosphorylation of the glucocorticoid
receptor in the prefrontal cortex, with no effect on corticosterone levels.
Second, neonatal LPS treatment had no effect on spatial memory in adolescence and
adulthood. However, a second challenge of LPS in adulthood impaired spatial
memory performance and neurogenesis and increased circulating levels of CCL2.
CONCLUSIONS: Our study shows for the first time, in mice, that a peripheral LPS
treatment at PND14 differentially alters emotional behaviors, but not spatial
memory, at adolescence and adulthood. The behavioral effect of LPS at PND14 could
be attributed to HPA axis deregulation and neurogenesis impairment.
PMID: 25224537 [Indexed for MEDLINE]