ArticleMolecular neurobiology2022
Downregulation of CRTC1 Is Involved in CUMS-Induced Depression-Like Behavior in the Hippocampus and Its RNA Sequencing Analysis.
Article in Molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- CREB: A Promising Therapeutic Target for Treating Psychiatric Disorders.Current neuropharmacology · 2024Pooled it
- Antidepressant Effects of L-Arginine and Its Role in Brain Energy MetabolismIranian biomedical journal · 2026Article
- Progress and challenges in exploring the pathogenesis of depressive disorders via RNA sequencing.Frontiers in genetics · 2026Review
- Exposure to childhood maltreatment is associated with specific epigenetic patterns in sperm.Molecular psychiatry · 2025Article
- Nrf2 activation rescues stress-induced depression-like behaviour and inflammatory responses in male but not female rats.Biology of sex differences · 2024Article
- Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems.CNS neuroscience & therapeutics · 2024Review
- High throughput mRNA sequencing reveals potential therapeutic targets of Si-Ni-San in the pons for a stress-induced depression model.Frontiers in pharmacology · 2024Article
- CRTC1 is a potential target to delay aging-induced cognitive deficit by protecting the integrity of the blood-brain barrier via inhibiting inflammation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic stress is an important risk factor for mood disorders including depression. The decreased level of CREB (cAMP-responsive element binding)-regulated transcription coactivator 1 (CRTC1) expression in hippocampus may be involved in depression-like behavior in some stress-induced depression models. But the mechanism of CRTC1 in mediating depression-like behavior remains unknown. In this study, chronic unpredictable mild stress (CUMS)-treated mice showed depression-like behavior accompanied by the downregulation of CRTC1 in the hippocampus. Adeno-associated virus (AAV)-CRTC1-mediated overexpression of CRTC1 in the hippocampus by stereotactic brain injection could significantly prevent depression-like behavior in CUMS-treated mice. The above data reveal that the downregulation of hippocampal CRTC1 expression participates in CUMS-induced depression-like behavior. In order to explore the key targets regulated by CRTC1, AAV-mediated CRTC1 short hairpin (shRNA) was constructed to achieve knockdown of CRTC1 in the hippocampus, and then the hippocampi were collected for RNA-sequencing (RNA-seq). The RNA-seq data show that upregulated genes were enriched in stress and immune system-associated GO terms and pathways such as response to stress and external stimulus and regulation of immune response and that downregulated genes were enriched in neural activity such as synaptic transmission and cognitive behavior. We further provided RT-qPCR data that the inflammation-related factors including Gpr84, Tlr2, Lyz2, and Icam1 were significantly upregulated in the hippocampus of both CUMS- and CRTC1 shRNA-induced models, some of them were also validated in protein levels by Western blotting. We propose a hypothesis that CUMS induces downregulation of CRTC1, which might lead to depression-like behavior via neuroinflammation pathway. This study provides new explanation for the inflammatory hypothesis of depression and some clues for exploring the molecular mechanism of CRTC1 regulation.
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