title: NCS-1 deficiency causes anxiety and depressive-like behavior with impaired non-aversive memory in mice.
abstract: Sensing and regulating intracellular levels of calcium are essential for proper cellular function. In neurons, calcium sensing plays important roles in neuronal plasticity, neurotransmitter release, long-term synapse modification and ion channel activity. Neuronal calcium sensor-1 (NCS-1) is a member of the highly conserved neuronal calcium sensor family. Although NCS-1 has been associated with psychiatric conditions including autism, bipolar disorder and schizophrenia, it is unclear which role NCS-1 plays in behavior. To understand the involvement of NCS-1 in psychiatric conditions, we provided a comprehensive behavioral characterization of NCS-1 knockout (KO) mice. These mice grow and develop normally without apparent abnormalities in comparison to wild type littermates. However, open field showed that NCS-1 deficiency impairs novelty-induced exploratory activity in both KO and heterozygote (HT) mice. Moreover, NCS-1-deficiency also resulted in anxiety- and depressive-like behaviors as demonstrated by elevated plus maze, large open field, forced swim and tail suspension tasks. Furthermore, based on spontaneous object recognition test, non-aversive long-term memory was impaired in NCS-1 KO mice. In contrast, neither social behavior nor a kind of aversive memory was affected under NCS-1 deficiency. These data implicate NCS-1 in exploratory activity, memory and mood-related behaviors, suggesting that NCS-1 gene ablation may result in phenotypic abnormalities associated with neuropsychiatric disorders.
authors.affiliation: Laboratório de Neurociência, INCT de Medicina Molecular, Departamento de Saúde Mental, Faculdade de Medicina da Universidade Federal de Minas Gerais, Av Alfredo Balena, 190, Belo Horizonte, 30130-100 MG, Brazil.
authors.forename: Vitor Bortolo
authors.initials: VB
authors.lastname: de Rezende
authors.affiliation: Laboratório de Neurociência, INCT de Medicina Molecular, Departamento de Saúde Mental, Faculdade de Medicina da Universidade Federal de Minas Gerais, Av Alfredo Balena, 190, Belo Horizonte, 30130-100 MG, Brazil.
authors.forename: Daniela Valadão
authors.initials: DV
authors.lastname: Rosa
authors.affiliation: Laboratório de Neurociências, INCT Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Bairro Universitário-C.P. 3167, 88806-000 Criciúma, SC, Brazil.
authors.forename: Clarissa Martinelli
authors.initials: CM
authors.lastname: Comim
authors.affiliation: Laboratório de Neurociência, INCT de Medicina Molecular, Departamento de Saúde Mental, Faculdade de Medicina da Universidade Federal de Minas Gerais, Av Alfredo Balena, 190, Belo Horizonte, 30130-100 MG, Brazil.
authors.forename: Luiz Alexandre Viana
authors.initials: LA
authors.lastname: Magno
authors.affiliation: Laboratório de Neurobiologia da Depressão, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Ana Lucia Severo
authors.initials: AL
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Patologia Molecular, Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina da Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, 30130-100 MG, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Vidigal
authors.affiliation: Banyan Biomarkers, Inc., Alachua, FL 32615, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeromin
authors.affiliation: Laboratório de Neurociências, INCT Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Bairro Universitário-C.P. 3167, 88806-000 Criciúma, SC, Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Laboratório de Neurociência, INCT de Medicina Molecular, Departamento de Saúde Mental, Faculdade de Medicina da Universidade Federal de Minas Gerais, Av Alfredo Balena, 190, Belo Horizonte, 30130-100 MG, Brazil. Electronic address: romano-silva@ufmg.br.
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Romano-Silva
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001008:Anxiety Disorders / Q000188:drug therapy / Q000503:physiopathology*; D001362:Avoidance Learning / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D003975:Diazepam / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000503:physiopathology*; D057567:Memory, Long-Term / Q000502:physiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051580:Neuronal Calcium-Sensor Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology; D012919:Social Behavior
chemical_list: D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins; D007099:Imipramine; D003975:Diazepam
keywords: Anxiety; Behavior; Depression; Knockout; Memory; NCS-1