title: Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in Rats.
abstract: Perinatal infection is a well-identified risk factor for a number of neurodevelopmental disorders, including brain white matter injury (WMI) and Autism Spectrum Disorders (ASD). The underlying mechanisms by which early life inflammatory events cause aberrant neural, cytoarchitectural, and network organization, remain elusive. This study is aimed to investigate how systemic lipopolysaccharide (LPS)-induced neuroinflammation affects microglia phenotypes and early neural developmental events in rats. We show here that LPS exposure at early postnatal day 3 leads to a robust microglia activation which is characterized with mixed microglial proinflammatory (M1) and anti-inflammatory (M2) phenotypes. More specifically, we found that microglial M1 markers iNOS and MHC-II were induced at relatively low levels in a regionally restricted manner, whereas M2 markers CD206 and TGFβ were strongly upregulated in a sub-set of activated microglia in multiple white and gray matter structures. This unique microglial response was associated with a marked decrease in naturally occurring apoptosis, but an increase in cell proliferation in the subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus. LPS exposure also leads to a significant increase in oligodendrocyte lineage population without causing discernible hypermyelination. Moreover, LPS-exposed rats exhibited significant impairments in communicative and cognitive functions. These findings suggest a possible role of M2-like microglial activation in abnormal neural development that may underlie ASD-like behavioral impairments.
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Yi
authors.identifier: http://orcid.org/0000-0003-0453-6921
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Roller
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Carter
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Ian
authors.initials: I
authors.lastname: Paul
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Abhay J
authors.initials: AJ
authors.lastname: Bhatt
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.|Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Rick C S
authors.initials: RC
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Lir-Wan
authors.initials: LW
authors.lastname: Fan
mesh_terms: D000819:Animal Communication; D000818:Animals; D000831:Animals, Newborn; D000067877:Autism Spectrum Disorder / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D066128:Gray Matter / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020547:Lateral Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D066127:White Matter / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta