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dc.contributor.authorSingh, Katyayani
dc.contributor.authorJayaram, Mohan
dc.contributor.authorKaare, Maria
dc.contributor.authorLeidmaa, Este
dc.contributor.authorJagomäe, Toomas
dc.contributor.authorHeinla, Indrek
dc.contributor.authorHickey, Miriam A.
dc.contributor.authorKaasik, Allen
dc.contributor.authorSchäfer, Michael K.
dc.contributor.authorInnos, Jürgen
dc.contributor.authorLilleväli, Kersti
dc.contributor.authorPhilips, Mari-Anne
dc.contributor.authorVasar, Eero
dc.date.accessioned2019-08-08T12:57:46Z
dc.date.available2019-08-08T12:57:46Z
dc.date.issued2019-04-01
dc.description.abstractNeuronal growth regulator 1 (NEGR1) belongs to the immunoglobulin (IgLON) superfamily of cell adhesion molecules involved in cortical layering. Recent functional and genomic studies implicate the role of NEGR1 in a wide spectrum of psychiatric disorders, such as major depression, schizophrenia and autism. Here, we investigated the impact of <i>Negr1</i> deficiency on brain morphology, neuronal properties and social behavior of mice. <i>In situ</i> hybridization shows <i>Negr1</i> expression in the brain nuclei which are central modulators of cortical-subcortical connectivity such as the island of Calleja and the reticular nucleus of thalamus. Brain morphological analysis revealed neuroanatomical abnormalities in <i>Negr1</i><sup>−</sup>/<sup>−</sup> mice, including enlargement of ventricles and decrease in the volume of the whole brain, corpus callosum, globus pallidus and hippocampus. Furthermore, decreased number of parvalbumin-positive inhibitory interneurons was evident in <i>Negr1</i><sup>−</sup>/<sup>−</sup> hippocampi. Behaviorally, <i>Negr1</i><sup>−</sup>/<sup>−</sup> mice displayed hyperactivity in social interactions and impairments in social hierarchy. Finally, <i>Negr1</i> deficiency resulted in disrupted neurite sprouting during neuritogenesis. Our results provide evidence that NEGR1 is required for balancing the ratio of excitatory/inhibitory neurons and proper formation of brain structures, which is prerequisite for adaptive behavioral profiles. Therefore, <i>Negr1</i><sup>−</sup>/<sup>−</sup> mice have a high potential to provide new insights into the neural mechanisms of neuropsychiatric disorders.en_US
dc.description.sponsorshipEstonian Research Council European Union through the European Regional Development Funden_US
dc.descriptionSource at <a href=https://doi.org/10.1038/s41598-019-41991-8>https://doi.org/10.1038/s41598-019-41991-8. </a>en_US
dc.identifier.citationSingh, K., Jayaram, M., Kaare, M., Leidmaa, E., Jagomäe, T., Heinla, I. ... Vasar, E. (2019). Neural cell adhesion molecule <i>Negr1</i> deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disorders. <i>Scientific Reports, 9</i>, 5457. https://doi.org/10.1038/s41598-019-41991-8en_US
dc.identifier.cristinIDFRIDAID 1692889
dc.identifier.doi10.1038/s41598-019-41991-8
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/10037/15875
dc.language.isoengen_US
dc.publisherNature Researchen_US
dc.relation.journalScientific Reports
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/692202/EU/Research capacity building through improved knowledge exchange and twinning frameworks for the Centre of Excellence in Translational Medicine//en_US
dc.relation.urihttps://doi.org/10.1038/s41598-019-41991-8
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Social science: 200::Psychology: 260en_US
dc.subjectVDP::Samfunnsvitenskap: 200::Psykologi: 260en_US
dc.titleNeural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disordersen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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