Altered Postnatal Cell Proliferation in Brains of Mouse Pups Prenatally Exposed to IgG from Mothers of Children with Autistic Disorder

Author:

Kadam Shilpa D.12,French Beth M.3,Kim S-T.1,Morris-Berry Christy M.3,Zimmerman Andrew W.4,Blue Mary E.125,Singer Harvey S.23

Affiliation:

1. Neuroscience Laboratory, Hugo W Moser Research Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

2. Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

3. Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

4. Department of Neurology and Developmental Medicine at Kennedy Krieger, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

5. Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Auto antibodies found in the mothers of children with autistic disorder (MCAD) when passively transferred to pregnant mice cause behavioral alterations in juvenile and adult offspring. The goal of this study was to identify whether intraperitoneal injection of MCAD-IgG during gestation affected postnatal cell proliferation and survival in P7 offspring. Pooled MCAD-IgG or IgG from mothers of unaffected children (MUC) or phosphate-buffered saline was injected daily into C57BL/J6 pregnant dams (gestational days E13–E18). MCAD-IgG exposure significantly increased cell proliferation in the subventricular and subgranular zones. In contrast, BrdU-labeled cells on P1 and surviving until P7 (P1-generated cells) showed reduced cell densities in layers 2–4 of frontal and parietal cortices of MCAD mice compared to those in MUC and PBS-injected mice. In conclusion, significant increases in cell proliferation at P7 and reduced densities of P1-generated cells distinguish in utero exposure to MCAD compared to MUC and PBS.

Publisher

SAGE Publications

Subject

General Neuroscience

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