title: Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice.
abstract: Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Sara Anna
authors.initials: SA
authors.lastname: Bonini
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mastinu
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Maccarinelli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mitola
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Premoli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Luca Rosario
authors.initials: LR
authors.lastname: La Rosa
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ferrari-Toninelli
authors.affiliation: Laboratory of Neuroplasticity, Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Grilli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D063928:Ependymoglial Cells / Q000378:metabolism / Q000473:pathology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D008297:Male; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D010320:Parvalbumins / Q000378:metabolism; D000091042:Reelin Protein; D018967:Risperidone / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism; D012919:Social Behavior; D013004:Somatostatin / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D014149:Tranquilizing Agents / Q000494:pharmacology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D052002:NF-kappa B p50 Subunit; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D000091042:Reelin Protein; D016704:Synapsins; D014149:Tranquilizing Agents; D013004:Somatostatin; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D018967:Risperidone
keywords: NF-κB; cortical structure; neurodevelopmental disorders; p50−/− mice; social behavior