Skip to Main content Skip to Navigation
Journal articles

Inflammation early in life is a vulnerability factor for emotional behavior at adolescence and for lipopolysaccharide-induced spatial memory and neurogenesis alteration at adulthood

Abstract : 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 ¿g/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 ¿/kg) was measured on spatial memory (Y-maze test), neurogenesis (doublecortin-positive cell numbers in the hippocampus) and plasma cytokine expression. 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.
Document type :
Journal articles
Complete list of metadata

https://hal.inrae.fr/hal-02632378
Contributor : Migration Prodinra <>
Submitted on : Wednesday, May 27, 2020 - 10:39:50 AM
Last modification on : Tuesday, July 6, 2021 - 2:54:04 PM

File

2014_Dinel_Journal of neuroinf...
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Anne-Laure Dinel, Corinne Joffre, Pierre Trifilieff, Agnès Aubert, Aline Foury, et al.. Inflammation early in life is a vulnerability factor for emotional behavior at adolescence and for lipopolysaccharide-induced spatial memory and neurogenesis alteration at adulthood. Journal of Neuroinflammation, BioMed Central, 2014, 11, 13 p. ⟨10.1186/s12974-014-0155-x⟩. ⟨hal-02632378⟩

Share

Metrics

Record views

22

Files downloads

55