ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2009
Suppression of the MEK/ERK signaling pathway reverses depression-like behaviors of CRF2-deficient mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 77 citations in OpenAlex.
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- Acupuncture may play a key role in anti-depression through various mechanisms in depression.Chinese medicine · 2024Review
- Follicle-stimulating hormone induces depression-like phenotype by affecting synaptic function.Frontiers in molecular neuroscience · 2024Article
- Article
- Causal effects of opioids on postpartum depression: a bidirectional, two-sample Mendelian randomization study.Frontiers in psychiatry · 2023Article
- Astrocyte metabolism and signaling pathways in the CNS.Frontiers in neuroscience · 2023Review
- Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress.Acta pharmacologica Sinica · 2022Article
- The role of circulatory systemic environment in predicting interferon-alpha-induced depression: The neurogenic process as a potential mechanism.Brain, behavior, and immunity · 2019Article
- The ERK Pathway: Molecular Mechanisms and Treatment of Depression.Molecular neurobiology · 2019Review
- Role of Corticotropin Releasing Factor in the Neuroimmune Mechanisms of Depression: Examination of Current Pharmaceutical and Herbal Therapies.Frontiers in cellular neuroscience · 2019Article
- CRHR1 Mediates the Up-Regulation of Synapsin I Induced by Nesfatin-1 Through ERK 1/2 Signaling in SH-SY5Y Cells.Cellular and molecular neurobiology · 2018Article
- Adenosine ATranslational psychiatry · 2017Article
- The CRF System as a Therapeutic Target for Neuropsychiatric Disorders.Trends in pharmacological sciences · 2016Review
- Transcriptomics in Interferon-α-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2016Article
- Regulation of ERK Kinase by MEK1 Kinase Inhibition in the Brain.The Journal of biological chemistry · 2015Article
- Fluoxetine signature on hippocampal MAPK signalling in sex-dependent manner.Journal of molecular neuroscience : MN · 2015Article
- Sustained AAV-mediated overexpression of CRF in the central amygdala diminishes the depressive-like state associated with nicotine withdrawal.Translational psychiatry · 2014Article
- The role of PKC signaling in CRF-induced modulation of startle.Psychopharmacology · 2013Article
- B-Raf and CRHR1 internalization mediate biphasic ERK1/2 activation by CRH in hippocampal HT22 Cells.Molecular endocrinology (Baltimore, Md.) · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The neuropeptide corticotropin-releasing factor (CRF) plays a critical role in the proper functioning of the stress response system through its actions on its receptors, CRF receptor 1 (CRF1) and CRF receptor 2 (CRF2), located at multiple anatomical sites. Clinical data indicate that stress response dysfunctions, such as excessive CRF activity and hyperstimulation of CRF1, are present in a range of stress-related disorders, including depression and anxiety disorders. Our previous work along with that of other laboratories has demonstrated that mice deficient in CRF2 (CRF2-/-) display increased anxiety and depression-like behaviors. In this study, we found CRF2-/- mice display increased hippocampal levels of activated (phosphorylated) mitogen-activated protein kinase (MAP kinase)/ERK kinase (MEK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and ribosomal protein S6 kinases 1 (RSK1). These changes can be explained by overactive hippocampal CRF1, in view of the finding that the application of the nonselective CRF receptor antagonist [Glu(11,16)] astressin ([Glu(11,16)]Ast) into the dorsal hippocampus of mutant mice returned the levels of the phosphorylated proteins to baseline. Moreover, inhibition of the hippocampal MEK/ERK pathway with the specific MEK inhibitor U0126, decreased depression-like behaviors in the forced swim test and tail suspension test of CRF2-/- mice. Similarly, treatment with [Glu(11,16)]Ast reversed depression phenotype of CRF2-/- mice without affecting the phenotype of wild-type littermates. Our results support an involvement of CRF receptors in the development of depression, such that elevated hippocampal CRF1 activity, in the absence of CRF2, produces a depression-dominated phenotype through the activation of the MEK/ERK pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.