Effects of Npas4 deficiency on anxiety, depression-like, cognition and sociability behaviour

Behav Brain Res. 2015 Mar 15:281:276-82. doi: 10.1016/j.bbr.2014.12.044. Epub 2014 Dec 27.

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.

Keywords: Anxiety; Depression; Memory; Neuronal PAS domain-containing protein 4; Sociability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Anxiety / psychology
  • Basic Helix-Loop-Helix Transcription Factors / deficiency*
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Behavior, Animal / physiology
  • Cognition / physiology*
  • Depression / genetics*
  • Depression / psychology
  • Heterozygote
  • Homozygote
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / genetics
  • Recognition, Psychology
  • Social Behavior*
  • Spatial Memory / physiology
  • Swimming / psychology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Npas4 protein, mouse