Molecular NeuroscienceAmygdaloid pERK1/2 in corticotropin-releasing hormone overexpressing mice under basal and acute stress conditions
Section snippets
Animals and housing
The generation of conditional CRH overexpressing (CRH-COE-Cam) mice as well as their genetic features has been previously described (Lu et al., 2008). Briefly, CRH-COE mice were established by introducing a single copy of the murine CRH cDNA, which is preceded by a loxP-flanked transcriptional terminator, into the ubiquitously expressed ROSA26 (R26) locus (Zambrowicz et al., 1997). Forebrain-restricted overexpression was achieved by breeding CRH-COE mice to transgenic CamK2a-cre mice (
Acute stress in CRH overexpressing mice results in decreased pERK1/2 levels in the BLA
Since the acute administration of CRH induces a limbic-specific ERK activation pattern restricted to the hippocampus and amygdala (Refojo et al., 2005), we analyzed the effect of chronic CRH overexpression on pERK1/2 immunoreactivity in these limbic areas in both control (CRH-COEcon-Cam) and CRH overexpressing (CRH-COEhom-Cam) mice on basal conditions and after 10 min of restraint stress. Brain slices of both genotypes in both experimental conditions were subjected to immunohistochemical
Discussion
In this work we evaluated for the first time pERK1/2 levels in a mouse model of limbic-restricted CRH overexpression. Previous work has shown that acute i.c.v. administration of CRH leads to a strong ERK1/2 activation in limbic areas (Refojo et al., 2005). Under basal conditions, CRH-COEhom-Cam mice exhibit levels of ERK1/2 activation in the BLA similar to those observed in control littermates. Restraint stress did not change pERK1/2 levels in the BLA of control animals, although the stress
Acknowledgments
We would like to thank Ursula Habersetzer, Sabrina Meyr, Tanja Orschmann and Stefanie Unkmeir for excellent technical assistance. This work was supported by grants from the university of Buenos Aires (UBA), the CONICET and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), Argentina, as well as by the Bundesministerium für Bildung und Forschung within the framework of NGFN-Plus (01GS08151 and 01GS08155). Part of the study was supported by the Freedom to Discover Award given by the
References (57)
- et al.
Role of extracellular signal-regulated kinase signal transduction pathway in anxiety
J Psychiatr Res
(2008) - et al.
CRF signaling: molecular specificity for drug targeting in the CNS
Trends Pharmacol Sci
(2006) - et al.
Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses?
Brain Res Brain Res Rev
(1990) - et al.
Acute hippocampal brain-derived neurotrophic factor restores motivational and forced swim performance after corticosterone
Biol Psychiatry
(2008) - et al.
HPA axis dysregulation in mice overexpressing corticotropin releasing hormone
Biol Psychiatry
(2002) - et al.
Transgenic overexpression of corticotropin releasing hormone provides partial protection against neurodegeneration in an in vivo model of acute excitotoxic stress
Neuroscience
(2008) - et al.
Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness
Front Neuroendocrinol
(2003) The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety
J Psychiatr Res
(1999)- et al.
Central CRH system in depression and anxiety—evidence from clinical studies with CRH1 receptor antagonists
Eur J Pharmacol
(2008) - et al.
The central corticotropin releasing factor system during development and adulthood
Eur J Pharmacol
(2008)
Distribution and expression of CRF receptor 1 and 2 mRNAs in the CRF over-expressing mouse brain
Brain Res
Region-specific effects of acute and repeated restraint stress on the phosphorylation of mitogen-activated protein kinases
Brain Res
Corticotropin-releasing hormone, arginine vasopressin, gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects
Biol Psychiatry
Essential role for TrkB receptors in hippocampus-mediated learning
Neuron
The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress
Behav Brain Res
Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development
Neuron
The role of corticotropin-releasing factor in depression and anxiety disorders
J Endocrinol
CRF and CRF receptors: role in stress responsivity and other behaviors
Annu Rev Pharmacol Toxicol
Brain region-specific neuroprotective action and signaling of corticotropin-releasing hormone in primary neurons
Endocrinology
Do centrally administered neuropeptides access cognate receptors?An analysis in the central corticotropin-releasing factor system
J Neurosci
Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression
J Neurosci
Immunocytochemical distribution of corticotropin-releasing hormone receptor type-1 (CRF(1))-like immunoreactivity in the mouse brain: light microscopy analysis using an antibody directed against the C-terminus
J Comp Neurol
Sensitive mRNA detection using unfixed tissue: combined radioactive and non-radioactive in situ hybridization histochemistry
Histochemistry
Stress and the brain: from adaptation to disease
Nat Rev Neurosci
Differential mRNA distribution of components of the ERK/MAPK signalling cascade in the adult mouse brain
J Comp Neurol
Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects
J Neurochem
The role of the extracellular signal-regulated kinase signaling pathway in mood modulation
J Neurosci
Immunolocalization of the mitogen-activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system
J Comp Neurol
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Sustained glucocorticoid exposure recruits cortico-limbic CRH signaling to modulate endocannabinoid function
2016, PsychoneuroendocrinologyCitation Excerpt :In the current study, however, given that sustained CORT exposure had no effect on amygdala 2-AG levels, but CRH overexpression did significantly increase amygdala 2-AG concentrations, it appears that certain biological changes associated with the CRH overexpressing mice may have contributed to these effects. The line of mutant mice we employed have higher levels of CRHR1 mRNA and protein expression in the basolateral amygdala (Lu et al., 2008; Silberstein et al., 2009), therefore a heightened CRHR1 signaling capacity may have contributed to the 2-AG differences observed in these mice. We also previously reported that intracerebroventricular administration of CRH was capable of increasing 2-AG content within the amygdala, although the temporal nature of this effect (2 h from onset) was much more delayed than the CRH-induced effects on FAAH/AEA dynamics.
CRHR1 mediates p53 transcription induced by high altitude hypoxia through ERK 1/2 signaling in rat hepatic cells
2013, PeptidesCitation Excerpt :The outcome of the GPCR pathway is the phosphorylation of a series of transcription factors and then transcriptional regulation of a series of genes. Although the CRHR1 pathway in rat liver has not been fully elucidated so far, CRH has been demonstrated to activate p-ERK 1/2 through CRHR1 in the central nervous system [34,38,46]. Our study also showed that CRHR1 on liver cells activated p-ERK 1/2 (Fig. 5B).
Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity
2012, PsychoneuroendocrinologyCitation Excerpt :In addition, we evaluated the expression levels of the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 (ERK1/2) in different brain regions. We focused on ERK1/2 because it plays an important role as an effector molecule in the actions of CRF in different brain regions, including the hippocampus and the amygdala (Refojo et al., 2005; Silberstein et al., 2009) and, in addition, because it has been suggested to play a role in stress, memory, plasticity and depression (Mazzucchelli and Brambilla, 2000; Shen et al., 2004; Qi et al., 2006; Reul and Chandramohan, 2007; Silberstein et al., 2009). A total of 156 adult male Sprague-Dawley rats (Charles River Laboratories, France) were used (approximately three months old and body weight of 250–275 g at the beginning of the experiment).
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2011, Behavioural Brain ResearchCitation Excerpt :The present results also show a slight enhancement of p-ERK2 expression in the BLA of naive stressed animals, indicating that prior exposure to restraint still activates the ERK signaling pathway, at least one day later. This activation is in agreement with a growing number of evidence showing that diverse types of acute stressors result in ERK activation in various brain structures, including the basolateral amygdala [46,53,58,60,61]. In most of these cases, the ERK1/2 levels were determined temporally close to the stressful experience.
Characterization of the B-Raf interactome in mouse hippocampal neuronal cells
2011, Journal of ProteomicsCitation Excerpt :Furthermore, since – unlike the ubiquitous Raf-1 – B-Raf is predominantly expressed in the nervous system [15], it constitutes a determining factor in the ability of neurons to activate ERK [16]. ERK activity in the central nervous system is linked to a variety of crucial molecular processes [17] and, in limbic areas, it was found to be modulated under different stress-related conditions in vivo [18,19]. More than 30 mutations in B-Raf have been associated with human cancers [20,21].
Characterization of a pachymedusa dacnicolor-sauvagine analog as a new high-affinity radioligand for corticotropin-releasing factor receptor studies
2015, Journal of Pharmacology and Experimental Therapeutics