title: Effects of Npas4 deficiency on anxiety, depression-like, cognition and sociability behaviour.
abstract: The transcription factor neuronal PAS domain-containing protein 4 (Npas4), which regulates the formation of inhibitory synapses on excitatory neurons, has been suggested as a candidate gene for neurological and psychiatric conditions such as bipolar depression, autism spectrum and cognitive disorders. A mouse model of Npas4 deficiency has been developed to investigate any role in these disorders. Behavioural characterisation of Npas4(-/-), Npas4(+/-) and Npas4(+/+) mice has been conducted using the open field, elevated zero maze (EZM), Y-maze, sociability test and forced swim test (FST) to investigate a range of behaviours. Npas4(-/-) mice spent more time in the open arm of the EZM than other genotypes, suggesting decreased anxiety-like behaviour. Npas4(+/-) mice, however, were more immobile in the FST than other genotypes, suggesting increased depression-like behaviour, and also showed impaired spatial recognition memory in the Y-maze. There were no differences between genotype in social behaviour. These results suggest that differential levels of Npas4 expression in the brain may regulate anxiety, depression and cognition related disorders.
authors.affiliation: Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Jaehne
authors.affiliation: Stroke Research Programme, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Klarić
authors.affiliation: Stroke Research Programme, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Koblar
authors.affiliation: Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: Discipline of Genetics, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: martin.lewis@sahmri.com.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000523:psychology; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency* / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D003863:Depression / Q000235:genetics* / Q000523:psychology; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D021641:Recognition, Psychology; D012919:Social Behavior; D065852:Spatial Memory / Q000502:physiology; D013550:Swimming / Q000523:psychology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C533005:Npas4 protein, mouse
keywords: Anxiety; Depression; Memory; Neuronal PAS domain-containing protein 4; Sociability