Chronic mild stress and imipramine treatment elicit opposite changes in behavior and in gene expression in the mouse prefrontal cortex

Erburu, M.M.; Cajaleon, L.; Guruceaga, Elizabeth; Venzala, E.; Muñoz-Cobo, I.; Beltrán, Elena; Puerta, Elena; Tordera, Rosa M.

doi:10.1016/j.pbb.2015.06.001

Cited by 31 publications

(24 citation statements)

References 80 publications

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“…Our findings demonstrate that the clock genes we studied are strongly expressed in the prefrontal cortex and, notably, they do not follow a diurnal rhythm (Figure 5A). This is in contrast to previously published data (Li et al, 2010; Edgar and McClung, 2013; Li et al, 2013; Erburu et al, 2015). However, the discrepancy probably relates to differences in the identity of the sub-regions being investigated.…”

Section: Discussioncontrasting

confidence: 99%

“…However, different stressors were applied, such as post-traumatic stress disorder (Koresh et al, 2012), severe stressors (chronic unpredictable stress; Jiang et al, 2013), and systemic glucocorticoid administration and restraint stress (Al-Safadi et al, 2014). Furthermore, the use of different strains of animals (Erburu et al, 2015; Schaufler et al, 2016) and time points of day for decapitation makes it difficult to compare our results with these studies.…”

Section: Discussionmentioning

confidence: 93%

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Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Christiansen

Bouzinova

Fahrenkrug

et al. 2016

IJNPPY

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Background:Abnormalities in circadian rhythms may be causal factors in development of major depressive disorder. The biology underlying a causal relationship between circadian rhythm disturbances and depression is slowly being unraveled. Although there is no direct evidence of dysregulation of clock gene expression in depressive patients, many studies have reported single-nucleotide polymorphisms in clock genes in these patients.Methods:In the present study we investigated whether a depression-like state in rats is associated with alternations of the diurnal expression of clock genes. The validated chronic mild stress (CMS) animal model of depression was used to investigate rhythmic expression of three clock genes: period genes 1 and 2 (Per1 and Per2) and Bmal1. Brain and liver tissue was collected from 96 animals after 3.5 weeks of CMS (48 control and 48 depression-like rats) at a 4h sampling interval within 24h. We quantified expression of clock genes on brain sections in the prefrontal cortex, nucleus accumbens, pineal gland, suprachiasmatic nucleus, substantia nigra, amygdala, ventral tegmental area, subfields of the hippocampus, and the lateral habenula using in situ hybridization histochemistry. Expression of clock genes in the liver was monitored by real-time quantitative polymerase chain reaction (PCR).Results:We found that the effect of CMS on clock gene expression was selective and region specific. Per1 exhibits a robust diurnal rhythm in most regions of interest, whereas Bmal1 and in particular Per2 were susceptible to CMS.Conclusion:The present results suggest that altered expression of investigated clock genes is likely associated with the induction of a depression-like state in the CMS model.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 93%

Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Christiansen

Bouzinova

Fahrenkrug

et al. 2016

IJNPPY

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“…The functional change in the post-synaptic density might be involved in the behavioral phenotypes in CMS-treated mice. The current findings regarding biological annotations were compared with Erburu’s study (Erburu et al, 2015) because the CMS protocol in the study was similar to ours, e.g., it used the same strain of mice (C57BL/6J), the same duration of the CMS (6 weeks), and the same bioinformatics (IPA). However, the gender of mice in the studies differed.…”

Section: Discussionmentioning

confidence: 66%

Gene expression alterations in the medial prefrontal cortex and blood cells in a mouse model of depression during menopause

Miyata

Kurachi

Sakurai

et al. 2016

Heliyon

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AimsThe prevalence of major depressive disorder (MDD) is higher in women than in men, and this may be due to the decline in estrogen levels that occurs during the menopausal transition. We studied the biological alterations in the medial prefrontal cortex (mPFC), which is a region that is highly implicated in the neurobiology of MDD, and the blood cells (BCs) of ovariectomized (OVX) mice subjected to chronic mild stress (CMS), which represents a mouse model of depression during menopause.Main methodsThe mPFC and the BCs were obtained from the same individuals. Gene expression levels were analyzed by microarray. The data were used for the Ingenuity Pathway Analysis and the Gene Ontology analysis.Key findingsThe gene expression alterations (GEAs) induced by OVX were mainly associated with ribosomal and mitochondrial functions in both the mPFC and the BCs. Rapamycin-insensitive companion of mTOR (RICTOR) was identified as a possible upstream regulator of the OVX-induced GEAs in both tissues. The CMS-induced GEAs were associated with retinoic acid receptor signaling, inflammatory cytokines and post-synaptic density in the mPFC, but not in the BCs.SignificanceOVX and CMS independently affect biological pathways in the mPFC, which is involved in the development of the depression-like phenotype. Because a subset of the OVX-induced GEAs in the mPFC also occurred in the BCs, the GEAs in the BCs might be a useful probe to predict biological pathways in the corresponding brain tissue under specific conditions such as OVX in females.

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“…Thus, dysfunction within the PFC can dramatically impact emotional regulation, attention, and cognition. Chronic stress, a known risk factor for neuropsychiatric disorders, induces profound impairments within the PFC, including dendritic atrophy (Liston et al., 2006, Izquierdo et al., 2006), changes in gene expression (Erburu et al., 2015), and impairments in long-term potentiation (Quan et al., 2011). In rodent models, exposure to prolonged, chronic stress leads to long-lasting changes in behavior (Elizalde et al., 2008, Matuszewich et al., 2007, Gourley and Taylor, 2009), making it an optimal model of stress-relevant neuropsychiatric disorders (Willner, 2016, Nestler and Hyman, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Ca v 1.2 channels are highly expressed throughout the forebrain (Hell et al., 1993) and in vitro studies have identified that disease-associated increases in Ca 2+ influx via Ca v 1.2 channels can alter gene expression patterns (Paşca et al., 2011, Tian et al., 2014) and contribute to activity dependent dendritic retraction (Krey et al., 2013), which has also been observed following chronic stress (Liston et al., 2006, Izquierdo et al., 2006, Erburu et al., 2015). In support of this, CACNA1C risk allele carriers show reduced PFC activity during working memory tasks, correlating with impaired performance (Bigos et al., 2010), and altered PFC structure (Wang et al., 2011) and connectivity (Wang et al., 2011, Paulus et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

Ca v 1.2 channels mediate persistent chronic stress-induced behavioral deficits that are associated with prefrontal cortex activation of the p25/Cdk5-glucocorticoid receptor pathway

Bavley

Fischer

Rizzo

et al. 2017

Neurobiology of Stress

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Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene CACNA1C, which codes for the Cav1.2 subunit of the L-type calcium channel (LTCC), as a common risk variant for multiple neuropsychiatric conditions. Cav1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways. Previous studies have found an association between stress and altered Cav1.2 expression in the brain, however the contribution of Cav1.2 channels to chronic stress-induced behaviors, and the precise Cav1.2 signaling mechanisms activated are currently unknown. Here we report that chronic stress leads to a delayed increase in Cav1.2 expression selectively within the prefrontal cortex (PFC), but not in other stress-sensitive brain regions such as the hippocampus or amygdala. Further, we demonstrate that while Cav1.2 heterozygous (Cav1.2+/−) mice show chronic stress-induced depressive-like behavior, anxiety-like behavior, and deficits in working memory 1–2 days following stress, they are resilient to the effects of chronic stress when tested 5–7 days later. Lastly, molecular studies find a delayed upregulation of the p25/Cdk5-glucocorticoid receptor (GR) pathway in the PFC when examined 8 days post-stress that is absent in Cav1.2+/− mice. Our findings reveal a novel Cav1.2-mediated molecular mechanism associated with the persistent behavioral effects of chronic stress and provide new insight into potential Cav1.2 channel mechanisms that may contribute to CACNA1C-linked neuropsychiatric phenotypes.

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Chronic mild stress and imipramine treatment elicit opposite changes in behavior and in gene expression in the mouse prefrontal cortex

Cited by 31 publications

References 80 publications

Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Gene expression alterations in the medial prefrontal cortex and blood cells in a mouse model of depression during menopause

Ca v 1.2 channels mediate persistent chronic stress-induced behavioral deficits that are associated with prefrontal cortex activation of the p25/Cdk5-glucocorticoid receptor pathway

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