title: Mapping pathological phenotypes in reelin mutant mice.
abstract: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders with multifactorial origin characterized by social communication deficits and the presence of repetitive behaviors/interests. Several studies showed an association between the reelin gene mutation and increased risk of ASD and a reduced reelin expression in some brain regions of ASD subjects, suggesting a role for reelin deficiency in ASD etiology. Reelin is a large extracellular matrix glycoprotein playing important roles during development of the central nervous system. To deeply investigate the role of reelin dysfunction as vulnerability factor in ASD, we assessed the behavioral, neurochemical, and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in the ultrasonic vocal repertoire and a general delay in motor development of reeler pups. We now report that adult male heterozygous (Het) reeler mice did not show social behavior and communication deficits during male-female social interactions. Wildtype and Het mice showed a typical light/dark locomotor activity profile, with a peak during the central interval of the dark phase. However, when faced with a mild stressful stimulus (a saline injection) only Het mice showed an over response to stress. In addition to the behavioral studies, we conducted high performance liquid chromatography and magnetic resonance imaging and spectroscopy to investigate whether reelin mutation influences brain monoamine and metabolites levels in regions involved in ASD. Low levels of dopamine in cortex and high levels of glutamate and taurine in hippocampus were detected in Het mice, in line with clinical data collected on ASD children. Altogether, our data detected subtle but relevant neurochemical abnormalities in reeler mice supporting this mutant line, particularly male subjects, as a valid experimental model to estimate the contribution played by reelin deficiency in the global ASD neurobehavioral phenotype.
authors.affiliation: Neurotoxicology and Neuroendocrinology Section, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , Rome , Italy ; Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome , Rome , Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Michetti
authors.affiliation: Behavioural Neuroscience Section, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , Rome , Italy ; Bambino Gesù Children's Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico , Rome , Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Romano
authors.affiliation: Molecular and Cellular Imaging Section, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Altabella
authors.affiliation: Neurotoxicology and Neuroendocrinology Section, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , Rome , Italy ; Department of Psychology, School of Behavioural Neuroscience, Sapienza University of Rome , Rome , Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Neurotoxicology and Neuroendocrinology Section, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Castelluccio
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome , Rome , Italy.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bedse
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome , Rome , Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
authors.affiliation: Molecular and Cellular Imaging Section, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Canese
authors.affiliation: Behavioural Neuroscience Section, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
authors.affiliation: Neurotoxicology and Neuroendocrinology Section, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Scattoni
keywords: autism spectrum disorders; circadian cycle; dopamine; glutamate; reeler mice; social interaction; stress response; ultrasonic vocalizations