title: Testing the correlation between experimentally-induced hypothyroidism during pregnancy and autistic-like symptoms in the rat offspring.
abstract: Thyroid hormones are important for the development of the central nervous system. Since the fetal thyroid gland is not functioning until mid-gestation, transport of maternal thyroid hormones across the placenta is essential during the early phases of gestation. Maternal thyroid deficiency has been associated with a higher incidence of neurodevelopmental disorders in the newborns. The relationship between maternal hypothyroidism and the onset of autism spectrum disorders (ASD) in the offspring, however, is still debated. To address this issue, we used a validated animal model of prenatal hypothyroidism based on the administration of the thyroid peroxidase inhibitor methimazole (MMI, 0.02g/100ml in tap water) to rat dams from gestational day 9 up to delivery. The offspring was tested in behavioral tasks during infancy (PNDs 5, 9, 13) and adolescence (PND 35-40) to capture some of the core and associated symptoms of ASD. MMI-exposed pups were able to vocalize as controls when separated from the nest, and showed intact social discrimination abilities in the homing behavior test. At adolescence, the offspring from both sexes did not show an anxious-phenotype in the elevated plus maze and showed intact object recognition. However, MMI-exposed male rats showed increased novelty-directed exploratory behaviors: they solicited their partner to play more and showed more interest for novel rather than familiar objects compared to control rats. Our results show that prenatal MMI-induced hypothyroidism does not cause in the rat offspring behaviors that resemble core and associated ASD symptoms, like deficits in communication and social interaction and anxiety.
authors.affiliation: Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Viale G. Marconi 446, 00146 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Melancia
authors.affiliation: Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Viale G. Marconi 446, 00146 Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Servadio
authors.affiliation: Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Viale G. Marconi 446, 00146 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Schiavi
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.affiliation: Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Viale G. Marconi 446, 00146 Rome, Italy; Laboratory of Translational Physiology, Department of Physiological Sciences, Federal University of Alfenas, Alfenas, Brazil. Electronic address: agiustipaiva@gmail.com.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Giusti-Paiva
authors.affiliation: Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Viale G. Marconi 446, 00146 Rome, Italy. Electronic address: viviana.trezza@uniroma3.it.
authors.forename: Viviana
authors.initials: V
authors.lastname: Trezza
mesh_terms: D000818:Animals; D001007:Anxiety; D001321:Autistic Disorder; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005260:Female; D007037:Hypothyroidism / Q000097:blood; D008297:Male; D008713:Methimazole; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D021641:Recognition, Psychology; D012919:Social Behavior; D013963:Thyroid Hormones / Q000097:blood; D014828:Vocalization, Animal
chemical_list: D013963:Thyroid Hormones; D008713:Methimazole
keywords: Autism spectrum disorders; Behavior; Maternal hypothyroidism; Methimazole; Rats