The circadian gene<i>Cryptochrome 2</i>influences stress‐induced brain activity and depressive‐like behavior in mice

Sokołowska, Ewa; Viitanen, Riikka; Misiewicz, Zuzanna; Mennesson, Marie; Saarnio, Suvi; Kulesskaya, Natalia; Kangsep, Sanna; Liljenbäck, Heidi; Marjamäki, Päivi; Autio, Anu; Callan, Saija-Anita; Nuutila, Pirjo; Roivainen, Anne; Partonen, Timo; Hovatta, Iiris

doi:10.1111/gbb.12708

Cited by 14 publications

(12 citation statements)

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“…Cry2 is crucial for normal emotional behavior and is directly associated with anxiety-like behavior [ 82 ] and as mentioned earlier, mice with higher anxiety behavior exhibit lower expression levels of Cry2 in the hippocampus in comparison with normal mice [ 50 ]. Moreover it has been found that ELF-EMF (50–60 Hz) can disturb circadian biorhythms by perturbation of the clock function of cryptochromes [ 83 ]; however, we did not find any significant Cry 2 alteration in any of the treatment groups.…”

Section: Discussionmentioning

confidence: 99%

Maternal stress induced anxiety-like behavior exacerbated by electromagnetic fields radiation in female rats offspring

et al. 2022

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There is a disagreement on whether extremely low frequency electromagnetic fields (ELF-EMF) have a beneficial or harmful effect on anxiety-like behavior. Prenatal stress induces frequent disturbances in offspring physiology such as anxiety-like behavior extending to adulthood. This study was designed to evaluate the effects of prenatal stress and ELF-EMF exposure before and during pregnancy on anxiety-like behavior and some anxiety-related pathways in the hippocampus of female rat offspring. A total of 24 female rats 40 days of age were distributed into four groups of 6 rats each: control, Stress (rats whose mothers underwent chronic stress), EMF (rats whose mothers were exposed to electromagnetic fields) and EMF/S (rats whose mothers were simultaneously exposed to chronic stress and ELF-EMF). The rats were given elevated plus-maze and open field tests and then their brains were dissected and their hippocampus were subjected to analysis. ELISA was used to measure 24(S)-hydroxy cholesterol, corticosterone, and serotonin levels. Cryptochrome2, steroidogenic acute regulatory protein, 3B-Hydroxy steroid dehydrogenase, N-methyl-D-aspartate receptor 2(NMDAr2) and phosphorylated N-methyl-D-aspartate receptor 2(PNMDAr2) were assayed by immunoblotting. Anxiety-like behavior increased in all treatment groups at the same time EMF increased anxiety induced by maternal stress in the EMF/S group. The stress group showed decreased serotonin and increased corticosterone levels. ELF-EMF elevated the PNMDAr2/NMDAr2 ratio and 24(S)-hydroxy cholesterol compared to the control group but did not change corticosterone. EMF did not restore changes induced by stress in behavioral and molecular tests. The results of the current study, clarified that ELF-EMF can induce anxiety-like behavior which may be attributed to an increase in the PNMDAr2/NMDAr2 ratio and 24(S)-OHC in the hippocampus, and prenatal stress may contribute to anxiety via a decrease in serotonin and an increase in corticosterone in the hippocampus. We also found that anxiety-like behavior induced by maternal stress exposure, is exacerbated by electromagnetic fields radiation.

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Section: Discussionmentioning

confidence: 99%

Maternal stress induced anxiety-like behavior exacerbated by electromagnetic fields radiation in female rats offspring

et al. 2022

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“…Anxiety-related behavioral tests are often performed together with depression tests in mouse models of neuropsychiatric disorders since anxiety usually co-morbids with depression (Cryan and Mombereau, 2004;Millstein and Holmes, 2007;Krishnan and Nestler, 2011;Jung et al, 2014;Belovicova et al, 2017;Sokolowska et al, 2021). Several behavioral tests based on the conflict between competing behaviors of exploring novel environments and avoiding potential threatening situations have been validated to assess anxiety, including the elevated plus maze (Pellow et al, 1985;Lister, 1987), open field (Treit and Fundytus, 1988), and light/dark box (Crawley and Goodwin, 1980;Crawley, 1981;Blumstein and Crawley, 1983), where our previous studies revealed sex differences in the open field and elevated plus maze tests with female C57BL/6N and FVB/N mice being less anxious (Eltokhi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Since anxiety-related behavioral tests are often performed together with depression tests in mouse models of neuropsychiatric disorders (Cryan and Mombereau, 2004;Millstein and Holmes, 2007;Krishnan and Nestler, 2011;Jung et al, 2014;Belovicova et al, 2017;Sokolowska et al, 2021), we extended our study and investigated sex differences in an anxiety test, the hyponeophagia test. Consistent with our previous study revealing sex differences in other anxiety tests in adolescent mice (Eltokhi et al, 2020), female C57BL/6N and DBA/2 mice showed an increased latency to drink the diluted milk compared to male mice at P27 (Trial 1: C57BL/6N: P = 0.006, DBA/2: P = 0.041 FVB/N: P = 0.99; Trial 2: C57BL/6N: P = 0.014, DBA/2: P = 0.027, FVB/N: P = 0.55; Figure 4A and Table 2).…”

Section: Anxiety-related Hyponeophagia Test At P27 and P37mentioning

confidence: 99%

Baseline Depression-Like Behaviors in Wild-Type Adolescent Mice Are Strain and Age but Not Sex Dependent

Eltokhi

Kurpiers

Pitzer

2021

Front. Behav. Neurosci.

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Depression is a major neuropsychiatric disorder, decreasing the ability of hundreds of millions of individuals worldwide to function in social, academic, and employment settings. Beyond the alarming public health problem, depression leads to morbidity across the entire age including adolescence and adulthood. Modeling depression in rodents has been used to understand the pathophysiological mechanisms behind this disorder and create new therapeutics. Although women are two times more likely to be diagnosed with depression compared to men, behavioral experiments on rodent models of depression are mainly performed in males based on the assumption that the estrous cycles in females may affect the behavioral outcome and cause an increase in the intrinsic variability compared to males. Still, the inclusion of female rodents in the behavioral analysis is mandatory to establish the origin of sex bias in depression. Here, we investigated the baseline depression-like behaviors in male and female mice of three adolescent wild-type inbred strains, C57BL/6N, DBA/2, and FVB/N, that are typically used as background strains for mouse models of neuropsychiatric disorders. Our experiments, performed at two different developmental stages during adolescence (P22–P26 and P32–P36), revealed strain but no sex differences in a set of depression-related tests, including tail suspension, sucrose preference and forced swim tests. Additionally, the 10-day interval during this sensitive period uncovered a strong impact on the behavioral outcome of C57BL/6N and FVB/N mice, highlighting a significant effect of maturation on behavioral patterns. Since anxiety-related behavioral tests are often performed together with depression tests in mouse models of neuropsychiatric disorders, we extended our study and included hyponeophagia as an anxiety test. Consistent with a previous study revealing sex differences in other anxiety tests in adolescent mice, male and females mice behaved differently in the hyponeophagia test at P27. Our study gives insight into the behavioral experiments assessing depression and stresses the importance of considering strain, age and sex when evaluating neuropsychiatric-like traits in rodent models.

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“…Cryptochromes are key proteins for the circadian clock 532 and SCN's intercellular networks development, which subserves coherent rhythm expression 533 . Furthermore, it is also shown that cryptochrome is associated with bipolar disorder disease [534][535][536][537] . In the context of animal magnetoreception, cryptochromes are the canonical magnetic sensing proteins (See Section 3.4) 44 , with flavin radicals playing a key role.…”

Section: Lithium Effects On Hyperactivitymentioning

confidence: 99%

Magnetic field effects in biology from the perspective of the radical pair mechanism

Zadeh-Haghighi¹,

Simon²

2022

Preprint

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A large and growing body of research shows that weak magnetic fields can significantly influence various biological systems, including plants, animals, and humans. However, the underlying mechanisms behind these phenomena remain elusive. It is remarkable that the magnetic energies implicated in these effects are much smaller than thermal energies. Here we review these observations, of which there are now hundreds, and we suggest that a viable explanation is provided by the radical pair mechanism, which involves the quantum dynamics of the electron and nuclear spins of naturally occurring transient radical molecules. While the radical pair mechanism has been studied in detail in the context of avian magnetoreception, the studies reviewed here show that magnetosensitivity is widespread throughout biology. We review magnetic field effects on various physiological functions, organizing them based on the type of the applied magnetic fields, namely static, hypomagnetic, and oscillating magnetic fields, as well as isotope effects. We then review the radical pair mechanism as a potential unifying model for the described magnetic field effects, and we discuss plausible candidate molecules that might constitute the radical pairs. We review recent studies proposing that the quantum nature of the radical pairs provides promising explanations for xenon anesthesia, lithium effects on hyperactivity, magnetic field and lithium effects on the circadian clock, and hypomagnetic field effects on neurogenesis and microtubule assembly. We conclude by discussing future lines of investigation in this exciting new area of quantum biology related to weak magnetic field effects.

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The circadian geneCryptochrome 2influences stress‐induced brain activity and depressive‐like behavior in mice

Cited by 14 publications

References 47 publications

Maternal stress induced anxiety-like behavior exacerbated by electromagnetic fields radiation in female rats offspring

Maternal stress induced anxiety-like behavior exacerbated by electromagnetic fields radiation in female rats offspring

Baseline Depression-Like Behaviors in Wild-Type Adolescent Mice Are Strain and Age but Not Sex Dependent

Magnetic field effects in biology from the perspective of the radical pair mechanism

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