Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in Rats
Autor: | Anna M. Roller, Kathleen Carter, Rick C.S. Lin, Ian A. Paul, Abhay J. Bhatt, Xuemei Dai, Lir-Wan Fan, Yi Pang |
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Rok vydání: | 2016 |
Předmět: |
Central Nervous System
Lipopolysaccharides Autism Spectrum Disorder lcsh:Medicine Apoptosis Immunostaining Nervous System Hippocampus Rats Sprague-Dawley Cognition 0302 clinical medicine Animal Cells Transforming Growth Factor beta Lateral Ventricles Medicine and Health Sciences Gray Matter lcsh:Science Cognitive Impairment Staining education.field_of_study Multidisciplinary Cell Death Microglia Cognitive Neurology Neurogenesis Brain White Matter Oligodendroglia medicine.anatomical_structure Neurology Cell Processes Cellular Types Anatomy Neural development Mannose Receptor Research Article Cognitive Neuroscience Cell Enumeration Techniques Population Subventricular zone Glial Cells Receptors Cell Surface Biology Research and Analysis Methods 03 medical and health sciences 030225 pediatrics medicine Animals Lectins C-Type education Microglial Cells Neuroinflammation Inflammation Behavior Dentate gyrus lcsh:R Biology and Life Sciences Cell Biology Oligodendrocyte Rats Animal Communication Mannose-Binding Lectins Animals Newborn Specimen Preparation and Treatment Dentate Gyrus Immunology Cognitive Science lcsh:Q Neuroscience 030217 neurology & neurosurgery |
Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 10, p e0164403 (2016) |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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