Reduced ventricular proliferation in the foetal cortex following maternal inflammation in the mouse
Open Access
- 29 September 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Brain
- Vol. 134 (11), 3236-3248
- https://doi.org/10.1093/brain/awr237
Abstract
It has been well established that maternal inflammation during pregnancy alters neurological function in the offspring, but its impact on cortical development and long-term consequences on the cytoarchitecture is largely unstudied. Here we report that lipopolysaccharide-induced systemic maternal inflammation in C57Bl/6 mice at embryonic Day 13.5 of pregnancy, as early as 8 h after challenge, caused a significant reduction in cell proliferation in the ventricular zone of the developing cerebral cortex, as revealed by quantification of anti-phospho-Histone H3 immunoreactivity and bromodeoxyuridine pulse labelling. The angle of mitotic cleavage, determined from analysis of haematoxylin and eosin staining, cyclin E1 gene expression and the pattern of β-catenin immunoreactivity were also altered by the challenge, which suggests a change from symmetric to asymmetric division in the radial progenitor cells. Modifications of cortical lamination and gene expression patterns were detected at post-natal Day 8 suggesting prolonged consequences of these alterations during embryonic development. Cellular uptake of proteins from the cerebrospinal fluid was observed in brains from lipopolysaccharide-treated animals in radial progenitor cells. However, the foetal blood–brain barrier to plasma proteins remained intact. Together, these results indicate that maternal inflammation can disrupt the ventricular surface and lead to decreased cellular proliferation. Changes in cell density in Layers IV and V at post-natal Day 8 show that these initial changes have prolonged effects on cortical organization. The possible shift in the fate of progeny and the resulting alterations in the relative cell numbers in the cerebral cortex following a maternal inflammatory response shown here will require further investigation to determine the long-term consequences of inflammation on the development of neuronal circuitry and behaviour.This publication has 55 references indexed in Scilit:
- Effects of Neonatal Systemic Inflammation on Blood-Brain Barrier Permeability and Behaviour in Juvenile and Adult RatsCardiovascular Psychiatry and Neurology, 2011
- The environment and susceptibility to schizophreniaProgress in Neurobiology, 2011
- Lissencephaly: Mechanistic insights from animal models and potential therapeutic strategiesSeminars in Cell & Developmental Biology, 2010
- Novel Embryonic Neuronal Migration and Proliferation Defects inDcxMutant Mice Are Exacerbated byLis1ReductionJournal of Neuroscience, 2010
- The ELGAN study of the brain and related disorders in extremely low gestational age newbornsEarly Human Development, 2009
- Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: Implications for genesis of neurodevelopmental disordersSchizophrenia Research, 2008
- Extrapolating brain development from experimental species to humansNeuroToxicology, 2007
- Breakdown of the blood–brain barrier to proteins in white matter of the developing brain following systemic inflammationCell and tissue research, 2005
- Synthesis of the foetal protein fetuin by early developing neurons in the immature neocortexJournal of Neurocytology, 1993
- Cell junctions and membrane specializations in the ventricular zone (germinal matrix) of the developing sheep brain: A CSF-brain barrierJournal of Neurocytology, 1987