Abnormal wake/sleep pattern in a novel gain-of-function model of DISC1

Abstract

Sleep disturbances are common in psychiatric disorders, but the causal relationship between the two and the underlying genetic factors is unclear. The DISC1 gene is strongly linked to mood disorders and schizophrenia in a Scottish pedigree. In an earlier study we found a sleep homeostasis disturbance in a Drosophila model overexpressing wild-type human DISC1. Here we aimed to explore the relationship between sleep and the DISC1 gene in a mammalian model, a novel transgenic mouse model expressing full-length human DISC1. We assessed circadian rhythms by monitoring wheel running activity under normal 24-h light:dark conditions and in constant darkness and found the DISC1 mice to have normal circadian photoentrainment and normal intrinsic circadian period. We also assessed sleep duration and quality in the DISC1 mice and found that they were awake longer than wild-type controls at baseline with a tendency for lower rebound of delta activity during recovery from a short sleep deprivation. Thus we suggest that DISC1 may be involved in sleep regulation.

Keywords: Behavior; Circadian rhythms; DISC1; Mouse model; Non rapid eye movement sleep; Rapid eye movement sleep; Sleep homeostasis.