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Acute in utero exposure to lipopolysaccharide induces inflammation in the pre-and postnatal brain and alters the glial cytoarchitecture in the developing amygdala

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Show simple item record O'Loughlin, Elaine Pakan, Janelle M. P. Yilmazer-Hanke, Deniz McDermott, Kieran W. 2017-12-20T10:13:52Z 2017-12-20T10:13:52Z 2017
dc.description peer-reviewed en_US
dc.description.abstract Background: Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders such as autism and schizophrenia, as well as seizure development. The amygdala is a brain region involved in the regulation of emotions, and amygdalar maldevelopment due to infection-induced MIA may lead to amygdala-related disorders. MIA priming of glial cells during development has been linked to abnormalities seen in later life; however, little is known about its effects on amygdalar biochemical and cytoarchitecture integrity. Methods: Time-mated C57BL6J mice were administered a single intraperitoneal injection of 50 μg/kg lipopolysaccharide (LPS) on embryonic day 12 (E12), and the effects of MIA were examined at prenatal, neonatal, and postnatal developmental stages using immunohistochemistry, real-time quantitative PCR, and stereological quantification of cytoarchitecture changes. Results: Fetal brain expression of pro-inflammatory cytokines (IL-1β, TNFα, and IL-6) was significantly upregulated at 4 h postinjection (E12) and remained elevated until the day of birth (P0). In offspring from LPS-treated dams, amygdalar expression of pro-inflammatory cytokines was also increased on day 7 (P7) and expression was sustained on day 40 (P40). Toll-like receptor (TLR-2, TLR-4) expression was also upregulated in fetal brains and in the postnatal amygdala in LPS-injected animals. Morphological examination of cells expressing ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) suggested long-term microglial activation and astrogliosis in postnatal amygdalar regions. Conclusions: Our results showed that LPS-induced MIA at E12 induces a pro-inflammatory cytokine profile in the developing fetal brain that continues up to early adulthood in the amygdala. Inflammation elicited by MIA may activate cells in the fetal brain and lead to alterations in glial (microglia and astrocyte) cells observed in the postnatal amygdala. Moreover, increased pro-inflammatory cytokines and their effects on glial subpopulations may in turn have deleterious consequences for neuronal viability. These MIA-induced changes may predispose offspring to amygdala-related disorders such as heightened anxiety and depression and also neurodevelopmental disorders, such as autism spectrum disorders. en_US
dc.language.iso eng en_US
dc.publisher BioMed Central en_US
dc.relation.ispartofseries Journal of Neuroinflammation;14:212
dc.subject maternal inflammation en_US
dc.subject amygdala en_US
dc.subject neuroinflammation en_US
dc.subject neurodevelopment en_US
dc.subject amygdalar development en_US
dc.subject inflammatory cytokines en_US
dc.subject microglia en_US
dc.subject Astrogliosis en_US
dc.subject lipopolysaccharide (LPS) en_US
dc.title Acute in utero exposure to lipopolysaccharide induces inflammation in the pre-and postnatal brain and alters the glial cytoarchitecture in the developing amygdala en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1186/s12974-017-0981-8
dc.contributor.sponsor HRB en_US
dc.relation.projectid Project HRA_POR/2010/159 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US

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