The circadian gene Cryptochrome 2 influences stress-induced brain activity and depressive-like behavior in mice

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Sokolowska , E , Viitanen , R , Misiewicz , Z , Mennesson , M , Saarnio , S , Kulesskaya , N , Kängsep , S , Liljenback , H , Marjamäki , P , Autio , A , Callan , S-A , Nuutila , P , Roivainen , A , Partonen , T & Hovatta , I 2021 , ' The circadian gene Cryptochrome 2 influences stress-induced brain activity and depressive-like behavior in mice ' , Genes, Brain and Behavior , vol. 20 , no. 4 , 12708 . https://doi.org/10.1111/gbb.12708

Title: The circadian gene Cryptochrome 2 influences stress-induced brain activity and depressive-like behavior in mice
Author: Sokolowska, Ewa; Viitanen, Riikka; Misiewicz, Zuzanna; Mennesson, Marie; Saarnio, Suvi; Kulesskaya, Natalia; Kängsep, Sanna; Liljenback, Heidi; Marjamäki, Paivi; Autio, Anu; Callan, Saija-Anita; Nuutila, Pirjo; Roivainen, Anne; Partonen, Timo; Hovatta, Iiris
Contributor: University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, National Institute for Health and Welfare (THL)
University of Helsinki, Department of Psychology and Logopedics
Date: 2021-04
Language: eng
Number of pages: 12
Belongs to series: Genes, Brain and Behavior
ISSN: 1601-1848
URI: http://hdl.handle.net/10138/335381
Abstract: Cryptochrome 2 (Cry2) is a core clock gene important for circadian regulation. It has also been associated with anxiety and depressive-like behaviors in mice, but the previous findings have been conflicting in terms of the direction of the effect. To begin to elucidate the molecular mechanisms of this association, we carried out behavioral testing, PET imaging, and gene expression analysis of Cry2(-/-) and Cry2(+/+) mice. Compared to Cry2(+/+) mice, we found that Cry2(-/-) mice spent less time immobile in the forced swim test, suggesting reduced despair-like behavior. Moreover, Cry2(-/-) mice had lower saccharin preference, indicative of increased anhedonia. In contrast, we observed no group differences in anxiety-like behavior. The behavioral changes were accompanied by lower metabolic activity of the ventro-medial hypothalamus, suprachiasmatic nuclei, ventral tegmental area, anterior and medial striatum, substantia nigra, and habenula after cold stress as measured by PET imaging with a glucose analog. Although the expression of many depression-associated and metabolic genes was upregulated or downregulated by cold stress, we observed no differences between Cry2(-/-) and Cry2(+/+) mice. These findings are consistent with other studies showing that Cry2 is required for normal emotional behavior. Our findings confirm previous roles of Cry2 in behavior and extend them by showing that the effects on behavior may be mediated by changes in brain metabolism.
Subject: anxiety
behavior
brain
brown adipose tissue
circadian rhythm
cryptochrome
depression
gene expression
PET
q&#8208
RT&#8208
PCR
CLOCK
MOUSE
CRY2
MODEL
515 Psychology
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