title: Prenatal stress increases the expression of proinflammatory cytokines and exacerbates the inflammatory response to LPS in the hippocampal formation of adult male mice.
abstract: Early life experiences, such as prenatal stress, may result in permanent alterations in the function of the nervous and immune systems. In this study we have assessed whether prenatal stress affects the inflammatory response of the hippocampal formation of male mice to an inflammatory challenge during adulthood. Pregnant C57BL/6 mice were randomly assigned to stress (n=10) or non-stress (n=10) groups. Animals of the stress group were placed in plastic transparent cylinders and exposed to bright light for 3 sessions of 45min every day from gestational day 12 to parturition. Non-stressed pregnant mice were left undisturbed. At four months of age, non stressed and prenatally stressed male offspring were killed, 24h after the systemic administration of lipopolysaccharide (LPS) or vehicle. Under basal conditions, prenatally stressed animals showed increased expression of interleukin 1β and tumor necrosis factor-α (TNF-α) in the hippocampus and an increased percentage of microglia cells with reactive morphology in CA1 compared to non-stressed males. Furthermore, prenatally stressed mice showed increased TNF-α immunoreactivity in CA1 and increased number of Iba-1 immunoreactive microglia and GFAP-immunoreactive astrocytes in the dentate gyrus after LPS administration. In contrast, LPS did not induce such changes in non-stressed animals. These findings indicate that prenatal stress induces a basal proinflammatory status in the hippocampal formation during adulthood that results in an enhanced activation of microglia and astrocytes in response to a proinflammatory insult.
authors.affiliation: Instituto Cajal, Avenida Doctor Arce 37, E-28002 Madrid, Spain. yolanda_diz@hotmail.com
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Diz-Chaves
authors.forename: Mariana
authors.initials: M
authors.lastname: Astiz
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Bellini
authors.forename: Luis M
authors.initials: LM
authors.lastname: Garcia-Segura
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D013315:Stress, Psychological / Q000276:immunology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone