title: Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.
abstract: Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor.
authors.affiliation: Department of Pathology and Laboratory Medicine.|MIND Institute.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, 95817, USA.
authors.forename: Verónica
authors.initials: V
authors.lastname: Martínez-Cerdeño
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, 95817, USA.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Camacho
authors.affiliation: MIND Institute.|Department of Rheumatology/Allergy and Clinical Immunology, UC Davis, Davis, CA 95616, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fox
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, 95817, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Miller
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, 95817, USA.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Ariza
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, 95817, USA.
authors.forename: Devon
authors.initials: D
authors.lastname: Kienzle
authors.affiliation: Department of Pathology and Laboratory Medicine.|Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, 95817, USA.
authors.forename: Kaela
authors.initials: K
authors.lastname: Plank
authors.affiliation: MIND Institute.|Department of Psychiatry and Behavioral Sciences, UC Davis, Sacramento, CA 95817, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Noctor
authors.affiliation: MIND Institute.|Department of Rheumatology/Allergy and Clinical Immunology, UC Davis, Davis, CA 95616, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Van de Water
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000378:metabolism; D005260:Female; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D009419:Nerve Tissue Proteins
keywords: autism; brain size; maternal autoantibody; neurogenesis; radial glial cells