title: Exposure to Folate Receptor Alpha Antibodies during Gestation and Weaning Leads to Severe Behavioral Deficits in Rats: A Pilot Study.
abstract: The central nervous system continues to develop during gestation and after birth, and folate is an essential nutrient in this process. Folate deficiency and folate receptor alpha autoantibodies (FRα-AuAb) have been associated with pregnancy-related complications and neurodevelopmental disorders. In this pilot study, we investigated the effect of exposure to FRα antibodies (Ab) during gestation (GST), the pre-weaning (PRW), and the post weaning (POW) periods on learning and behavior in adulthood in a rat model. In the open field test and novel object recognition task, which examine locomotor activity and anxiety-like behavior, deficits in rats exposed to Ab during gestation and pre-weaning (GST+PRW) included more time spent in the periphery or corner areas, less time in the central area, frequent self-grooming akin to stereotypy, and longer time to explore a novel object compared to a control group; these are all indicative of increased levels of anxiety. In the place avoidance tasks that assess learning and spatial memory formation, only 30% of GST+PRW rats were able to learn the passive place avoidance task. None of these rats learned the active place avoidance task indicating severe learning deficits and cognitive impairment. Similar but less severe deficits were observed in rats exposed to Ab during GST alone or only during the PRW period, suggesting the extreme sensitivity of the fetal as well as the neonatal rat brain to the deleterious effects of exposure to Ab during this period. Behavioral deficits were not seen in rats exposed to antibody post weaning. These observations have implications in the pathology of FRα-AuAb associated with neural tube defect pregnancy, preterm birth and neurodevelopmental disorders including autism.
authors.affiliation: Departments of Medicine, State University New York (SUNY)-Downstate Medical Center, Brooklyn, New York, 11209, United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Sequeira
authors.affiliation: The School of Graduate Studies, State University New York (SUNY)-Downstate Medical Center, Brooklyn, New York, 11209, United States of America.
authors.forename: Ankuri
authors.initials: A
authors.lastname: Desai
authors.affiliation: Preventive Medicine and Public Health and IISPV Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Berrocal-Zaragoza
authors.affiliation: Preventive Medicine and Public Health and IISPV Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Murphy
authors.affiliation: Preventive Medicine and Public Health and IISPV Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
authors.forename: Joan D
authors.initials: JD
authors.lastname: Fernandez-Ballart
authors.affiliation: Departments of Medicine, State University New York (SUNY)-Downstate Medical Center, Brooklyn, New York, 11209, United States of America.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Quadros
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000008:administration & dosage* / Q000276:immunology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003072:Cognition Disorders / Q000503:physiopathology; D005260:Female; D058975:Folate Receptor 1 / Q000008:administration & dosage / Q000276:immunology*; D005492:Folic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D009436:Neural Tube Defects / Q000473:pathology; D010865:Pilot Projects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D014886:Weaning
chemical_list: D001323:Autoantibodies; D058975:Folate Receptor 1; D005492:Folic Acid