Casein kinase 1 epsilon and circadian misalignment impact affective behaviours in mice. (23rd September 2021)

• Record Type: Journal Article
• Authors: Zhou, Lili; Fitzpatrick, Karrie; Olker, Christopher; Vitaterna, Martha H.; Turek, Fred W.
• Other Names: Schmidt Mathias V. guestEditor.; Robinson Oliver guestEditor.; Sandi Carmen guestEditor.
• Is Part Of: European journal of neuroscience. Volume 55:Number 9/10(2022)
• Page Start: 2939
• Page End: 2954
• Publication Date: 2021-09-23
• Subjects: anxiety -- circadian rhythms -- Csnk1e -- despair -- fear; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15456
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Affective behaviours and mental health are profoundly affected by disturbances in circadian rhythms. Casein kinase 1 epsilon (CSNK1E) is a core component of the circadian clock. Mice with tau or null mutation of this gene have shortened and lengthened circadian period respectively. Here, we examined anxiety‐like, fear, and despair behaviours in both male and female mice of these two different mutants. Compared with wild‐type mice, we found reductions in fear and anxiety‐like behaviours in both mutant lines and in both sexes, with the tau mutants exhibiting the greatest phenotypic changes. However, the behavioural despair had distinct phenotypic patterns, with markedly less behavioural despair in female null mutants, but not in tau mutants of either sex. To determine whether abnormal light entrainment of tau mutants to 24‐h light–dark cycles contributes to these phenotypic differences, we also examined these behaviours in tau mutants on a 20‐h light–dark cycle close to their endogenous circadian period. The normalized entrainment restored more wild‐type‐like behaviours for fear and anxiety, but it induced behavioural despair in tau mutant females. These data show that both mutations of Csnk1e broadly affect fear and anxiety‐like behaviours, while the effects on behavioural despair vary with genetics, photoperiod, and sex, suggesting that the mechanisms by which Csnk1e affects fear and anxiety‐like behaviours may be similar, but distinct from those affecting behavioural despair. Our study also provides experimental evidence in support of the hypothesis of beneficial outcomes from properly entrained circadian rhythms in terms of the anxiety‐like and fear behaviours. Abstract : Anxiety‐like, fear, and despair behaviours were examined in both male and female mice of Csnk1e wild type, null, and tau mutants. Compared with wild‐type mice, lower levels of fear and anxiety‐like behaviours were observed in both mutant lines and in both sexes. However, the behavioural despair had distinct phenotypic patterns, with markedly less behavioural despair in female null mutants, but not in tau mutant s of either sex. To determine whether abnormal light entrainment of tau mutants to 24‐h light–dark cycles contributes to these phenotypic differences, these behaviours were also examined in tau mutants on a 20‐h light–dark cycle close to their endogenous circadian period. The normalized entrainment restored more wild‐type‐like behaviours for fear and anxiety, but it induced behavioural despair in tau mutant females.