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
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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