Acute and chronic stress differentially regulate cyclin-dependent kinase 5 in mouse brain: implications to glucocorticoid actions and major depression

Papadopoulou, Anna; Siamatras, Thomas; Delgado-Morales, Raúl; Amin, Niranjana D.; Shukla, Vibha; Zheng, Yali; Pant, Harish C.; Almeida, Osborne F. X.; Kino, Tomoshige

doi:10.1038/tp.2015.72

Cited by 53 publications

(43 citation statements)

References 70 publications

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“…Bagot et al (71) have used a model based on a social-interaction paradigm, subjecting the mice to a chronic social defeat stress to induce a depression-like state. This is likely to induce transcriptional responses that differ from our mice, because we used an experimental paradigm that does not include chronic stress (72). Notwithstanding, because both paradigms used KT as an antidepressant, we found important similarities in KT-related gene responses.…”

Section: Discussionmentioning

confidence: 99%

A Circadian Genomic Signature Common to Ketamine and Sleep Deprivation in the Anterior Cingulate Cortex

Orozco-Solís

Montellier

Aguilar-Arnal

et al. 2017

Biological Psychiatry

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BACKGROUND Conventional antidepressants usually require several weeks to achieve a full clinical response in patients with major depressive disorder, an illness associated with dysregulated circadian rhythms and a high incidence of suicidality. Two rapid-acting antidepressant strategies, low-dose ketamine (KT) and sleep deprivation (SD) therapies, dramatically reduce depressive symptoms within 24 hours in a subset of major depressive disorder patients. However, it is unknown whether they exert their actions through shared regulatory mechanisms. To address this question, we performed comparative transcriptomics analyses to identify candidate genes and relevant pathways common to KT and SD. METHODS We used the forced swim test, a standardized behavioral approach to measure antidepressant-like activity of KT and SD. We investigated gene expression changes using high-density microarrays and pathway analyses (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis) in KT- and SD-treated mice compared with saline-treated control male mice. RESULTS We show that KT and SD elicit common transcriptional responses implicating distinct elements of the circadian clock and processes involved in neuronal plasticity. There is an overlap of 64 genes whose expression is common in KT and SD. Specifically, there is downregulation of clock genes including Ciart, Per2, Npas4, Dbp, and Rorb in both KT- and SD-treated mice. CONCLUSIONS We demonstrate a potential involvement of the circadian clock in rapid antidepressant responses. These findings could open new research avenues to help design chronopharmacological strategies to treat major depressive disorder.

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Section: Discussionmentioning

confidence: 99%

A Circadian Genomic Signature Common to Ketamine and Sleep Deprivation in the Anterior Cingulate Cortex

Orozco-Solís

Montellier

Aguilar-Arnal

et al. 2017

Biological Psychiatry

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“…cDNA was synthesized using the TaqMan Reverse Transcription Reagents and oligo-dT as a primer (Applied Biosystems, Foster City, CA, USA). PCR was then performed in the 7 500 Real-time PCR System (Applied Biosystems), as previously described [27,28]. Primer pairs for quantifying the levels of Gas5 and the ribosomal S18 component used in SYBR Green real-time PCR were; Gas5: forward primer: 5′-TCTGAGCAGGAATGGCAGTGT-3′, reverse primer: 5′-CATCCTCCTTTGCCACAGAACT-3′; S18: forward primer: 5′-GTGGAGCGATTTGTCTGGTT-3′, reverse primer: 5′-CGCTGAGCCAGTCAGTGTAG-3′.…”

Section: Sybr Green Real-time Pcr Analysismentioning

confidence: 99%

Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases

2016

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Glucocorticoids have strong regulatory actions on the immune system and act as potent therapeutic compounds for autoimmune and inflammatory diseases. We previously reported that the long noncoding RNA growth arrest-specific 5 (Gas5), which accumulates inside the cells in response to cellular starvation/growth arrest, functions as a potent repressor of the glucocorticoid receptor (GR) through its RNA "glucocorticoid response element (GRE)". To evaluate potential roles of Gas5 in immune-related disorders, we examined Gas5 RNA levels in various autoimmune, inflammatory, and infectious diseases using the microarray data available in the Gene Expression Omnibus. We found that Gas5 levels were altered in whole blood or leukocytes of the patients with rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and sarcoidosis. Gas5 levels were also altered in infectious diseases, such as by the human immunodeficiency virus type-1 and influenza virus, and bacterial sepsis. In our experimental analysis using mice, Gas5 levels were kept at high basal levels and did not respond to fasting in immune organs, such as spleen and thymus, while its levels in metabolic organs, including liver, fat, and skeletal muscles, were low at baseline and were highly elevated upon this treatment, possibly through suppression of the mTOR pathway. These results suggest that Gas5 plays a role in the regulation of immune functions and pathogenesis/pathophysiology of autoimmune, inflammatory, and infectious diseases in part through modulation of the GR transcriptional activity via its decoy RNA "GRE". Changes in the Gas5 levels may also influence disease response to immunosuppressive glucocorticoid therapy.

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“…Complex interactions between different targets, cell types and layers of epigenetic regulation may facilitate wide, indirect effects of environmental stress [7,12]. Beyond these critical effects on brain and behaviour, stress may also be expected to have far-reaching effects on wholeorganism physiology, including immunity, metabolism, nutrition and reproduction, but these remain largely unexplored [16].…”

Section: Introductionmentioning

confidence: 99%

Contrasting effects of acute and chronic stress on the transcriptome, epigenome, and immune response of Atlantic salmon

et al. 2018

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Stress experienced during early life may have lasting effects on the immune system, with impacts on health and disease dependent on the nature and duration of the stressor. The epigenome is especially sensitive to environmental stimuli during early life and represents a potential mechanism through which stress may cause long-lasting health effects. However, the extent to which the epigenome responds differently to chronic vs acute stressors is unclear, especially for nonmammalian species. We examined the effects of acute stress (cold-shock during embryogenesis) and chronic stress (absence of tank enrichment during larval-stage) on global gene expression (using RNA-seq) and DNA methylation (using RRBS) in the gills of Atlantic salmon (Salmo salar) four months after hatching. Chronic stress induced pronounced transcriptional differences, while acute stress caused few lasting transcriptional effects. However, both acute and chronic stress caused lasting and contrasting changes in the methylome. Crucially, we found that acute stress enhanced transcriptional immune response to a pathogenic challenge (bacterial lipopolysaccharide, LPS), while chronic stress suppressed it. We identified stress-induced changes in promoter and gene-body methylation that were associated with altered expression for a small proportion of immune-related genes, and evidence of wider epigenetic regulation within signalling pathways involved in immune response. Our results suggest that stress can affect immuno-competence through epigenetic mechanisms, and highlight the markedly different effects of chronic larval and acute embryonic stress. This knowledge could be used to harness the stimulatory effects of acute stress on immunity, paving the way for improved stress and disease management through epigenetic conditioning.

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Acute and chronic stress differentially regulate cyclin-dependent kinase 5 in mouse brain: implications to glucocorticoid actions and major depression

Cited by 53 publications

References 70 publications

A Circadian Genomic Signature Common to Ketamine and Sleep Deprivation in the Anterior Cingulate Cortex

A Circadian Genomic Signature Common to Ketamine and Sleep Deprivation in the Anterior Cingulate Cortex

Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases

Contrasting effects of acute and chronic stress on the transcriptome, epigenome, and immune response of Atlantic salmon

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