INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Prenatal stress increases the expression of proinflammatory cytokines and exarcebates the inflammatory response to lipopolysaccharide (LPS) in the hippocampal formation of adult female mice
Autor/es:
DIZ-CHAVES Y; ASTIZ M; BELLINI MJ; GARCIA-SEGURA LM
Lugar:
TORINO, ITALIA
Reunión:
Congreso; 7TH MEETING STEROIDS AND NERVOUS SYSTEM; 2013
Resumen:
It is known that development and plasticity of the neuroendocrine system can be affected by many factors, and that adverse events during the prenatal period can result in long-lasting changes in adulthood [1-3]. Indeed, prenatal stress results in an enhancement of certain aspects of immune function, including elevated levels of inflammatory cytokines in the periphery and in the brain [4-6]. This proinflammatory status of prenatally stressed animals may affect normal brain function, since cytokines such as IL6, IL-1β and TNF-α have different physiological roles, including regulation of neuronal development, ionic homeostasis, neuropeptide release and synaptic plasticity [7-10]. In addition, cytokines could take part in the pathogenesis and progression of neurodegenerative diseases [11-12]. 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. Methods: Animals used in our experiments were derived from four different reproductions performed at separated seasonal periods throughout the year. Adult virgin C57BL/6 female mice (2 months of age) from the Complutense University animal colony were group-housed (6 per cage) to coordinate their estrous cycle. Females in estrous were individually housed for 24h in the presence of a sexually experienced male. Females were then examined to detect for the possible presence of a vaginal plug, which was used to confirm mating. Pregnant mice were randomly assigned to stress (n=10) or nonstress (n=10) groups. Animals of the stress group were placed in plastic transparent cylinders and exposed to bright light for 3 sessions of 45 min every day from gestational day 12 to parturition. Nonstressed 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. Plasma corticosterone was measured by radioimmuneassay. Interleukin 1β (IL1β) and tumor necrosis factor-α (TNF-α) levels were assessed in the hippocampus by quantitative real-time polymerase chain reaction. Immunohistochemistry analysis for Iba1 (marker of microglia) and GFAP (marker of astroglia) and TNF alpha were performed. Also the morphology of microglia was assessed. Results: 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. Conclusion: 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. References [1] Darnaudéry, M., Maccari, S., 2008. Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Research Reviews 57, 571-85 [2] de Kloet, E.R., Joëls, M., Holsboer, F., 2005. Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 6, 463-75. [3] Weinstock, 2005. Weinstock, M., 2005. The potential influence of maternal stress hormones on evelopment and mental health of the offspring. 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