Increased microglial activation in the rat brain following neonatal exposure to a bacterial mimetic

Sominsky, Luba; Walker, Adam K.; Ong, Lin Kooi; Tynan, Ross; Walker, Frederick R.; Hodgson, Deborah M.

doi:10.1016/j.bbr.2011.08.038

Cited by 56 publications

(53 citation statements)

References 33 publications

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“…Because microglia can self-renew for CNS maintenance [47,65], early insults may have a long-lived impact. Notably, in perinatal bacterial infection models, microglial Iba1 immunoreactivity was associated with increased anxiety and elevated brain IL-1β levels that corresponded with decreased memory after lipopolysaccharide (LPS) challenge [35,43,66]. Isolated CD11b + microglia from LPS injected mice, previously exposed to perinatal infection, demonstrated increased IL-1β secretion, supporting the idea that early exposure to inflammation has long- lasting consequences on microglial reactivity [43].…”

Section: Discussionmentioning

confidence: 95%

Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring

Kang

Kurti

Fair

et al. 2014

J Neuroinflammation

123

101

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Obesity induces a low-grade inflammatory state and has been associated with behavioral and cognitive alterations. Importantly, maternal environmental insults can adversely impact subsequent offspring behavior and have been linked with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (AHDH). It is unknown if maternal obesity significantly alters offspring sociability, a key ASD feature, and if altering maternal diet will provide an efficacious intervention paradigm for behavioral deficits. Here we investigated the impact of maternal high fat diet (HFD) and maternal dietary intervention during lactation on offspring behavior and brain inflammation in mice. We found that maternal HFD increased anxiety and decreased sociability in female offspring. Additionally, female offspring from HFD-fed dams also exhibited increased brain IL-1β and TNFα and microglial activation. Importantly, maternal dietary intervention during lactation was sufficient to alleviate social deficits and brain inflammation. Maternal obesity during gestation alone was sufficient to increase hyperactivity in male offspring, a phenotype that was not ameliorated by dietary intervention. These data suggest that maternal HFD acts as a prenatal/perinatal insult that significantly impacts offspring behavior and inflammation and that dietary intervention during lactation may be an easily translatable, efficacious intervention to offset some of these manifestations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0156-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 95%

Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring

Kang

Kurti

Fair

et al. 2014

J Neuroinflammation

123

101

View full text Add to dashboard Cite

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“…4). Each stimulus (MS, LPS) increases the inflammatory state of the brain at an early age, which is thought to continue into adulthood [50]. The double insult MS-LPS could worsen the vulnerability of the individual, which is predicted by the MS model, leading to cognitive and emotional alterations in adulthood.…”

Section: Discussionmentioning

confidence: 99%

Early Life Stress Activates Glial Cells in the Hippocampus but Attenuates Cytokine Secretion in Response to an Immune Challenge in Rat Pups

Saavedra

Navarro²,

Torner³

2017

Neuroimmunomodulation

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Objective: Early life stress (ELS) increases the vulnerability to developing psychopathological disorders in adulthood that are accompanied by brain inflammatory processes. However, it is not known how a combined double hit (stress and immune) at an early age affects the response of the neuroimmune system. Here we investigated the effect of periodic maternal separation (MS) followed by administration of lipopolysaccharide (LPS) on glial cells in the CA3 region and hilus of the hippocampus and on cytokine release on postnatal day (PN) 15. Methods: Male rat pups were subjected to MS (3 h/day, PN1-14). MS and control pups received a single LPS injection (1 mg/kg of body weight) on PN14. They were subjected to an open field test 1 h later. The pups were sacrificed 90 min after LPS injection (PN14) or on PN15 for cytokine or immunohistological analyses, respectively. Results: LPS reduced the locomotion and induced high corticosterone levels in treated pups. MS or LPS reduced microglial density and activated microglial cells in the hippocampal CA3 and hilus regions. Microglial activation was highest in MS-LPS pups. The astrocyte density was mildly reduced by MS or LPS in the CA3 region and hilus, but the reduction was maximal in MS-LPS pups. LPS increased the secretion of plasmatic interleukin (IL)-1β, tumor necrosis factor-α, and IL-6, and of hippocampal IL-1β protein, but these were attenuated in MS-LPS pups. Conclusion: Although MS and LPS activate neuroimmune cells, stress attenuates the hippocampal and peripheral cytokine response to LPS through an as-yet unidentified adaptive mechanism. These results provide information regarding the neurobiology of stress and inflammation.

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“…Inflammatory responses associated with perinatal LPS exposure have been implicated in long-term programming of a variety of physiological and behavioural outcomes, such as adult immune responses [54,55,56,57], metabolic function [58,59] and neurobehavioural outcomes [60,61,62]. Only a few studies, however, have investigated the impact of perinatal immune challenge on reproduction.…”

Section: Early-life Programming Of Health and Diseasementioning

confidence: 99%

Factors in Early-Life Programming of Reproductive Fitness

2015

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Fertility rates have been declining worldwide, with a growing number of young women suffering from infertility. Infectious and inflammatory diseases are important causes of infertility, and recent evidence points to the critical role of the early-life microbial environment in developmental programming of adult reproductive fitness. Our laboratory and others have demonstrated that acute exposure to an immunological challenge early in life has a profound and prolonged impact on male and female reproductive development. This review presents evidence that perinatal exposure to immunological challenge by a bacterial endotoxin, lipopolysaccharide, acts at all levels of the hypothalamic-pituitary-gonadal axis, resulting in long-lasting changes in reproductive function, suggesting that disposition to infertility may begin early in life.

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Increased microglial activation in the rat brain following neonatal exposure to a bacterial mimetic

Cited by 56 publications

References 33 publications

Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring

Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring

Early Life Stress Activates Glial Cells in the Hippocampus but Attenuates Cytokine Secretion in Response to an Immune Challenge in Rat Pups

Factors in Early-Life Programming of Reproductive Fitness

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