The medulla oblongata shows a sex-specific inflammatory response to systemic neonatal lipopolysaccharide
Early life inflammation has been linked to long-term modulation of behavioural outcomes due to the central nervous system, but it is now becoming apparent it is also linked to dysfunction of visceral physiology. The medulla oblongata contains a number of nuclei critical for homeostasis, therefore we...
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creator | Hedley, Kateleen E. Cuskelly, Annalisa Callister, Robert J. Horvat, Jay C. Hodgson, Deborah M. Tadros, Melissa A. |
description | Early life inflammation has been linked to long-term modulation of behavioural outcomes due to the central nervous system, but it is now becoming apparent it is also linked to dysfunction of visceral physiology. The medulla oblongata contains a number of nuclei critical for homeostasis, therefore we utilised the well-established model of neonatal lipopolysaccharide (LPS) exposure to examine the immediate and long-term impacts of systemic inflammation on the medulla oblongata. Wistar rats were injected with LPS or saline on postnatal days 3 and 5, with tissues collected on postnatal days 7 or 90 in order to assess expression of inflammatory mediators and microglial morphology in autonomic regions of the medulla oblongata. We observed a distinct sex-specific response of all measured inflammatory mediators at both ages, as well as significant neonatal sex differences in inflammatory mediators within saline groups. At both ages, microglial morphology had significant changes in branch length and soma size in a sex-specific manner in response to LPS exposure. This data not only highlights the strong sex-specific response of neonates to LPS administration, but also the significant life-long impact on the medulla oblongata and the potential altered control of visceral organs.
•Using a rodent model of neonatal immune activation found sex-specific changes to gene expression and microglia.•Sex-specific upregulation of inflammatory mediators in the medulla oblongata at acute and long-term timepoints.•Fundamental sex-differences between saline groups at acute and long-term•Sex-specific changes to microglia provide a potential contributory mechanism |
doi_str_mv | 10.1016/j.jneuroim.2024.578316 |
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•Using a rodent model of neonatal immune activation found sex-specific changes to gene expression and microglia.•Sex-specific upregulation of inflammatory mediators in the medulla oblongata at acute and long-term timepoints.•Fundamental sex-differences between saline groups at acute and long-term•Sex-specific changes to microglia provide a potential contributory mechanism</description><identifier>ISSN: 0165-5728</identifier><identifier>ISSN: 1872-8421</identifier><identifier>EISSN: 1872-8421</identifier><identifier>DOI: 10.1016/j.jneuroim.2024.578316</identifier><identifier>PMID: 38394966</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Animals, Newborn ; Autonomic ; Brainstem ; Female ; Inflammation - metabolism ; Inflammation Mediators - metabolism ; Lipopolysaccharide ; Lipopolysaccharides - metabolism ; Lipopolysaccharides - toxicity ; Male ; Medulla Oblongata ; Rats ; Rats, Wistar ; Sex-specific</subject><ispartof>Journal of neuroimmunology, 2024-04, Vol.389, p.578316, Article 578316</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-b231553c596a3404d636340cda64f8d1ff3532bc069cb687156006923ac3abbd3</citedby><cites>FETCH-LOGICAL-c416t-b231553c596a3404d636340cda64f8d1ff3532bc069cb687156006923ac3abbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jneuroim.2024.578316$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38394966$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hedley, Kateleen E.</creatorcontrib><creatorcontrib>Cuskelly, Annalisa</creatorcontrib><creatorcontrib>Callister, Robert J.</creatorcontrib><creatorcontrib>Horvat, Jay C.</creatorcontrib><creatorcontrib>Hodgson, Deborah M.</creatorcontrib><creatorcontrib>Tadros, Melissa A.</creatorcontrib><title>The medulla oblongata shows a sex-specific inflammatory response to systemic neonatal lipopolysaccharide</title><title>Journal of neuroimmunology</title><addtitle>J Neuroimmunol</addtitle><description>Early life inflammation has been linked to long-term modulation of behavioural outcomes due to the central nervous system, but it is now becoming apparent it is also linked to dysfunction of visceral physiology. The medulla oblongata contains a number of nuclei critical for homeostasis, therefore we utilised the well-established model of neonatal lipopolysaccharide (LPS) exposure to examine the immediate and long-term impacts of systemic inflammation on the medulla oblongata. Wistar rats were injected with LPS or saline on postnatal days 3 and 5, with tissues collected on postnatal days 7 or 90 in order to assess expression of inflammatory mediators and microglial morphology in autonomic regions of the medulla oblongata. We observed a distinct sex-specific response of all measured inflammatory mediators at both ages, as well as significant neonatal sex differences in inflammatory mediators within saline groups. At both ages, microglial morphology had significant changes in branch length and soma size in a sex-specific manner in response to LPS exposure. This data not only highlights the strong sex-specific response of neonates to LPS administration, but also the significant life-long impact on the medulla oblongata and the potential altered control of visceral organs.
•Using a rodent model of neonatal immune activation found sex-specific changes to gene expression and microglia.•Sex-specific upregulation of inflammatory mediators in the medulla oblongata at acute and long-term timepoints.•Fundamental sex-differences between saline groups at acute and long-term•Sex-specific changes to microglia provide a potential contributory mechanism</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Autonomic</subject><subject>Brainstem</subject><subject>Female</subject><subject>Inflammation - metabolism</subject><subject>Inflammation Mediators - metabolism</subject><subject>Lipopolysaccharide</subject><subject>Lipopolysaccharides - metabolism</subject><subject>Lipopolysaccharides - toxicity</subject><subject>Male</subject><subject>Medulla Oblongata</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Sex-specific</subject><issn>0165-5728</issn><issn>1872-8421</issn><issn>1872-8421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtu2zAQRYmiQeM8fiHgshs5fEvatTDaJoCBbJI1QVGjmIYkqhyprf8-DGx3m9Xl4twZziHkjrM1Z9zc79f7EZYUw7AWTKi1LivJzSey4lUpikoJ_pmsMqgLXYrqklwh7hnjWqr6C7mUlaxVbcyK7J53QAdol753NDZ9HF_d7Cju4l-kOeFfgRP40AVPw9j1bhjcHNOBJsApjgh0jhQPOMOQiRHimOs97cMUp9gf0Hm_cym0cEMuOtcj3J7ymrz8_PG8eSi2T78eN9-3hVfczEUjJNdael0bJxVTrZEmp2-dUV3V8q6TWorGM1P7xlQl14blt5DOS9c0rbwmX49zpxR_L4CzHQJ6yOflzy1oJZNKqKrmZUbNEfUpIibo7JTC4NLBcmbfLdu9PVu275bt0XIu3p12LE1297921pqBb0cA8qV_AiSLPsDooQ0J_GzbGD7a8QbRTJOF</recordid><startdate>20240415</startdate><enddate>20240415</enddate><creator>Hedley, Kateleen E.</creator><creator>Cuskelly, Annalisa</creator><creator>Callister, Robert J.</creator><creator>Horvat, Jay C.</creator><creator>Hodgson, Deborah M.</creator><creator>Tadros, Melissa A.</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20240415</creationdate><title>The medulla oblongata shows a sex-specific inflammatory response to systemic neonatal lipopolysaccharide</title><author>Hedley, Kateleen E. ; Cuskelly, Annalisa ; Callister, Robert J. ; Horvat, Jay C. ; Hodgson, Deborah M. ; Tadros, Melissa A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-b231553c596a3404d636340cda64f8d1ff3532bc069cb687156006923ac3abbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Autonomic</topic><topic>Brainstem</topic><topic>Female</topic><topic>Inflammation - metabolism</topic><topic>Inflammation Mediators - metabolism</topic><topic>Lipopolysaccharide</topic><topic>Lipopolysaccharides - metabolism</topic><topic>Lipopolysaccharides - toxicity</topic><topic>Male</topic><topic>Medulla Oblongata</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Sex-specific</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hedley, Kateleen E.</creatorcontrib><creatorcontrib>Cuskelly, Annalisa</creatorcontrib><creatorcontrib>Callister, Robert J.</creatorcontrib><creatorcontrib>Horvat, Jay C.</creatorcontrib><creatorcontrib>Hodgson, Deborah M.</creatorcontrib><creatorcontrib>Tadros, Melissa A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hedley, Kateleen E.</au><au>Cuskelly, Annalisa</au><au>Callister, Robert J.</au><au>Horvat, Jay C.</au><au>Hodgson, Deborah M.</au><au>Tadros, Melissa A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The medulla oblongata shows a sex-specific inflammatory response to systemic neonatal lipopolysaccharide</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2024-04-15</date><risdate>2024</risdate><volume>389</volume><spage>578316</spage><pages>578316-</pages><artnum>578316</artnum><issn>0165-5728</issn><issn>1872-8421</issn><eissn>1872-8421</eissn><abstract>Early life inflammation has been linked to long-term modulation of behavioural outcomes due to the central nervous system, but it is now becoming apparent it is also linked to dysfunction of visceral physiology. The medulla oblongata contains a number of nuclei critical for homeostasis, therefore we utilised the well-established model of neonatal lipopolysaccharide (LPS) exposure to examine the immediate and long-term impacts of systemic inflammation on the medulla oblongata. Wistar rats were injected with LPS or saline on postnatal days 3 and 5, with tissues collected on postnatal days 7 or 90 in order to assess expression of inflammatory mediators and microglial morphology in autonomic regions of the medulla oblongata. We observed a distinct sex-specific response of all measured inflammatory mediators at both ages, as well as significant neonatal sex differences in inflammatory mediators within saline groups. At both ages, microglial morphology had significant changes in branch length and soma size in a sex-specific manner in response to LPS exposure. This data not only highlights the strong sex-specific response of neonates to LPS administration, but also the significant life-long impact on the medulla oblongata and the potential altered control of visceral organs.
•Using a rodent model of neonatal immune activation found sex-specific changes to gene expression and microglia.•Sex-specific upregulation of inflammatory mediators in the medulla oblongata at acute and long-term timepoints.•Fundamental sex-differences between saline groups at acute and long-term•Sex-specific changes to microglia provide a potential contributory mechanism</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>38394966</pmid><doi>10.1016/j.jneuroim.2024.578316</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Animals, Newborn Autonomic Brainstem Female Inflammation - metabolism Inflammation Mediators - metabolism Lipopolysaccharide Lipopolysaccharides - metabolism Lipopolysaccharides - toxicity Male Medulla Oblongata Rats Rats, Wistar Sex-specific |
title | The medulla oblongata shows a sex-specific inflammatory response to systemic neonatal lipopolysaccharide |
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