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Corticotropin releasing factor

Julie E Finnell, Brandon L Muniz, Akhila R Padi, Calliandra M Lombard, Casey M Moffitt, Christopher S Wood, L Britt Wilson, Lawrence P Reagan, Marlene A Wilson, Susan K Wood
BACKGROUND: Women are at greater risk than men of developing depression and comorbid disorders such as cardiovascular disease. This enhanced risk begins at puberty and ends following menopause, suggesting a role for ovarian hormones in this sensitivity. Here we used a model of psychosocial witness stress in female rats to determine the stress-induced neurobiological adaptations that underlie stress susceptibility in an ovarian hormone-dependent manner. METHODS: Intact or ovariectomized (OVX) female rats were exposed to five daily 15-minute witness-stress exposures...
January 31, 2018: Biological Psychiatry
M Tavares-Silva, D Ferreira, S Cardoso, A R Raimundo, J Barbosa-Breda, A Leite-Moreira, A Rocha-Sousa
Urocortin 2 (UCN2) is a peptide related to corticotropin-releasing factor, capable of activating CRF-R2. Among its multisystemic effects, it has actions in all 3 muscle subtypes. This study's aim was to determine its potential role in two of the intrinsic eye muscle kinetics. Strips of iris sphincter (rabbit) and ciliary (bovine) muscles were dissected and mounted in isometric force-transducer systems filled with aerated-solutions. Contraction was elicited using carbachol (10(-6) M for iris sphincter, 10(-5) M for ciliary muscle), prior to all testing substances...
March 12, 2018: Physiological Research
Paula G Slater, Sebastian E Gutierrez-Maldonado, Katia Gysling, Carlos F Lagos
The corticotropin-releasing factor (CRF) system is a key mediator of the stress response and addictive behavior. The CRF system includes four peptides: The CRF system includes four peptides: CRF, urocortins I-III, CRF binding protein (CRF-BP) that binds CRF with high affinity, and two class B G-protein coupled receptors CRF1 R and CRF2 R. CRF-BP is a secreted protein without significant sequence homology to CRF receptors or to any other known class of protein. Recently, it has been described a potentiation role of CRF-BP over CRF signaling through CRF2 R in addictive-related neuronal plasticity and behavior...
2018: Frontiers in Endocrinology
Jorge Tovar-Díaz, Matthew B Pomrenze, Russell Kan, Bahram Pahlavan, Hitoshi Morikawa
Stressful events rapidly trigger activity-dependent synaptic plasticity, driving the formation of aversive memories. However, it remains unclear how stressful experience affects plasticity mechanisms to regulate appetitive learning, such as intake of addictive drugs. Using rats, we show that corticotropin-releasing factor (CRF) and α1 adrenergic receptor (α1AR) signaling enhance the plasticity of NMDA-receptor-mediated glutamatergic transmission in ventral tegmental area (VTA) dopamine (DA) neurons through distinct effects on inositol 1,4,5-triphosphate (IP3 )-dependent Ca2+ signaling...
March 6, 2018: Cell Reports
Michael E Authement, Ludovic D Langlois, Ryan D Shepard, Caroline A Browne, Irwin Lucki, Haifa Kassis, Fereshteh S Nugent
Centrally released corticotropin-releasing factor or hormone (extrahypothalamic CRF or CRH) in the brain is involved in the behavioral and emotional responses to stress. The lateral habenula (LHb) is an epithalamic brain region involved in value-based decision-making and stress evasion. Through its inhibition of dopamine-mediated reward circuitry, the increased activity of the LHb is associated with addiction, depression, schizophrenia, and behavioral disorders. We found that extrahypothalamic CRF neurotransmission increased neuronal excitability in the LHb...
March 6, 2018: Science Signaling
Carolina L Haass-Koffler
The corticotropin releasing factor (CRF) exerts its effects by acting on its receptors and on the binding protein (CRFBP). Extensive literature suggests a role of CRF in alcohol use disorder (AUD). Less is known about the specific role, if any, of CRFBP in AUD. In this review, we summarize recent interdisciplinary efforts toward identifying the contribution of CRFBP in mediating CRF activation. The role of CRFBP in alcohol-related behaviors has been evaluated with the ultimate goal of designing effective novel therapeutic strategies for AUD...
October 13, 2017: Alcohol
Laurie L Wellman, Mairen E Fitzpatrick, Amy M Sutton, Brook L Williams, Mayumi Machida, Larry D Sanford
The basolateral nucleus of the amygdala (BLA) plays a significant role in mediating individual differences in the effects of fear memory on sleep. Here, we assessed the effects of antagonizing corticotropin releasing factor receptor 1 (CRFR1) after shock training (ST) on fear-conditioned behaviors and sleep. Outbred Wistar rats were surgically implanted with electrodes for recording EEG and EMG and with bilateral guide cannulae directed at BLA. Data loggers were placed intraperitoneally to record core body temperature...
March 1, 2018: Hormones and Behavior
Marian L Logrip, John R Walker, Lydia O Ayanwuyi, Valentina Sabino, Roberto Ciccocioppo, George F Koob, Eric P Zorrilla
Alcoholism is a pervasive societal problem, yet available pharmacotherapies fail to treat most sufferers. The type 1 corticotropin-releasing factor (CRF1 ) receptor has received much attention for its putative role in the progression to alcohol dependence, although at present its success in clinical trials has been limited. Two single-nucleotide polymorphisms in the rat Crhr1 promoter have been identified in the Marchigian substrain of Sardinian alcohol-preferring (msP) rats. Unlike other Wistar-derived alcohol-preferring lines, nondependent msP rats reduce their alcohol self-administration in response to CRF1 antagonists and show increased brain CRF1 expression...
2018: Frontiers in Psychiatry
Mahanand Chatoo, Yi Li, Zhiqiang Ma, John Coote, Jizeng Du, Xuequn Chen
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder defined by ROME IV criteria as pain in the lower abdominal region, which is associated with altered bowel habit or defecation. The underlying mechanism of IBS is not completely understood. IBS seems to be a product of interactions between various factors with genetics, dietary/intestinal microbiota, low-grade inflammation, and stress playing a key role in the pathogenesis of this disease. The crosstalk between the immune system and stress in IBS mechanism is increasingly recognized...
2018: Frontiers in Endocrinology
Stefanie M Klampfl, Milena M Schramm, Barbara M Gaßner, Katharina Hübner, Audrey F Seasholtz, Paula J Brunton, Doris S Bayerl, Oliver J Bosch
Maternal behavior and anxiety are potently modulated by the brain corticotropin-releasing factor (CRF) system postpartum. Downregulation of CRF in limbic brain regions is essential for appropriate maternal behavior and an adaptive anxiety response. Here, we focus our attention on arguably the most important brain region for maternal behavior, the hypothalamic medial preoptic area (MPOA). Within the MPOA, mRNA for CRF receptor subtype 1 (protein: CRFR1, gene: Crhr1) was more abundantly expressed than for subtype 2 (protein: CRFR2, gene: Crhr2), however expression of Crhr1, Crhr2 and CRF binding-protein (protein: CRFBP, gene: Crhbp) mRNA was similar between virgin and lactating rats...
February 22, 2018: Neuropharmacology
Mariela Faykoo-Martinez, D Ashley Monks, Iva B Zovkic, Melissa M Holmes
The social environment can alter pubertal timing through neuroendocrine mechanisms that are not fully understood; it is thought that stress hormones (e.g., glucocorticoids or corticotropin-releasing hormone) influence the hypothalamic-pituitary-gonadal axis to inhibit puberty. Here, we use the eusocial naked mole-rat, a unique species in which social interactions in a colony (i.e. dominance of a breeding female) suppress puberty in subordinate animals. Removing subordinate naked mole-rats from this social context initiates puberty, allowing for experimental control of pubertal timing...
2018: PloS One
Angela N Pierce, Olivia C Eller-Smith, Julie A Christianson
AIMS: Patients with interstitial cystitis/painful bladder syndrome (IC/PBS) commonly suffer from widespread pain and mood disorder, which has been attributed to improper functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Voluntary exercise has been shown to improve HPA axis function, therefore we are determining whether voluntary wheel running can attenuate urological pain and dysfunction following neonatal maternal separation (NMS) in female mice. METHODS: Mice underwent NMS for 3 h/day from postnatal Day 1-21, were caged with free access to running wheels at 4 weeks of age, and assessed 4 weeks later for bladder sensitivity, micturition, reward behavior, mast cell degranulation, and HPA axis-related in vitro analysis...
February 21, 2018: Neurourology and Urodynamics
A Pietrelli, M Di Nardo, A Masucci, A Brusco, N Basso, L Matkovic
The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age) of age. Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system...
February 17, 2018: Neuroscience
Takuto Kojima, Michiyo Mochizuki, Takafumi Takai, Yasutaka Hoashi, Sachie Morimoto, Masaki Seto, Minoru Nakamura, Katsumi Kobayashi, Yuu Sako, Maiko Tanaka, Naoyuki Kanzaki, Yohei Kosugi, Takahiko Yano, Kazuyoshi Aso
A new class of corticotropin releasing factor 1 (CRF1 ) receptor antagonists characterized by a tricyclic core ring was designed and synthesized. Novel tricyclic derivatives 2a-e were designed as CRF1 receptor antagonists based on conformation analysis of our original 2-anilinobenzimidazole CRF1 receptor antagonist. The synthesized tricyclic derivatives 2a-e showed CRF1 receptor binding activity with IC50 values of less than 400 nM, and the 1,2,3,4-tetrahydropyrimido-[1,2-a]benzimidazole derivative 2e was selected as a lead compound with potent in vitro CRF1 receptor binding activity (IC50 = 7...
February 8, 2018: Bioorganic & Medicinal Chemistry
Carolin Leistner, Andreas Menke
Stress is a state of derailed homeostasis and a main environmental risk factor for psychiatric diseases. Chronic or uncontrollable stress may lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is a common feature of stress-related psychiatric disorders. One of the key mechanisms underlying a disturbed HPA axis is an impaired function of the glucocorticoid receptor (GR) with an enhanced or reduced feedback sensitivity for glucocorticoids and subsequently altered concentrations of peripheral cortisol...
February 2, 2018: Psychoneuroendocrinology
Kenneth M McCullough, Filomene G Morrison, Jakob Hartmann, William A Carlezon, Kerry J Ressler
Molecular identification and characterization of fear controlling circuitries is a promising path towards developing targeted treatments of fear-related disorders. Three-color in situ hybridization analysis was used to determine whether somatostatin (SOM, Sst ), neurotensin (NTS, Nts ), corticotropin-releasing factor (CRF, Crf ), tachykinin 2 (TAC2, Tac2 ), protein kinase c-δ (PKC-δ, Prkcd ), and dopamine receptor 2 (DRD2, Drd2 ) mRNA colocalize in male mouse amygdala neurons. Expression and colocalization was examined across capsular (CeC), lateral (CeL), and medial (CeM) compartments of the central amygdala...
January 2018: ENeuro
Esfandiar Azadmarzabadi, Arvin Haghighatfard, Alireza Mohammadi
BACKGROUND: In stressful situations, a person's ability to appropriately complete tasks with minimal anxiety is known as stress resilience. Genetic variants in neuropeptide Y, Corticotropin releasing hormone receptor 1 (CRHR1), and serotonin transporter have been previously reported to be associated with low resilience, but the relationship between low resilience and the dopaminergic signalling pathway is not well understood. Here, we aimed to describe the association between comprehensive psychological characteristics and messenger RNA levels of dopamine receptor D1 (DRD1), dopamine receptor D2 (DRD2), dopamine receptor D3 (DRD3), dopamine receptor D4 (DRD4), dopamine receptor D5 (DRD5), COMT, Dopamine Beta-Hydroxylase (DBH), Tyrosine hydroxylase (TH), monoamine oxidase A (MAOM), dopa decarboxylase (DDC), dopamine transporter (DAT), serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) genes based on peripheral blood samples from 400 subjects who react differently to major life event stressors...
February 8, 2018: Psychogeriatrics: the Official Journal of the Japanese Psychogeriatric Society
Seiichi Yakabi, Lixin Wang, Hiroshi Karasawa, Pu-Qing Yuan, K Koike, Koji Yakabi, Yvette F Tache
We investigated whether vasoactive intestinal peptide (VIP) and/or prostaglandins contribute to peripheral corticotropin-releasing factor (CRF)-induced CRF1 receptor mediated stimulation of colonic motor function and diarrhea in rats. The VIP antagonist, [4Cl-D-Phe 6 , Leu 17 ]VIP injected intraperitoneally (ip) completely prevented CRF (10 µg/kg, ip)-induced fecal output and diarrhea occurring within the first hour post injection whereas pretreatment with the prostaglandin synthesis inhibitor, indomethacin had no effect...
February 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Diego Andolina, Matteo Di Segni, Alessandra Accoto, Luisa Lo Iacono, Antonella Borreca, Donald Ielpo, Nicola Berretta, Emerald Perlas, Stefano Puglisi-Allegra, Rossella Ventura
Recent studies show that microRNA-34 (miR-34) family is critical in the regulation of stress response also suggesting that it may contribute to the individual responsiveness to stress. We have recently demonstrated that mice carrying a genetic deletion of all miR-34 isoforms (triple knockout, TKO) lack the stress-induced serotonin (5-HT) and GABA release in the medial prefrontal cortex (mpFC) and basolateral amygdala (BLA), respectively. Here, we evaluated if the absence of miR-34 was also able to modify the stress-coping strategy in the forced swimming test...
February 7, 2018: Molecular Neurobiology
Leandro A Oliveira, Lucas Gomes-de-Souza, Ricardo Benini, Carlos C Crestani
The aims of the present study were to assess an interaction of corticotropin-releasing factor (CRF) neurotransmission within the bed nucleus of the stria terminalis (BNST) with local nitrergic signaling, as well as to investigate an involvement of activation of local NMDA glutamate receptor and nitric oxide (NO) signaling in control of cardiovascular responses to acute restraint stress by BNST CRF neurotransmission in rats. We observed that CRF microinjection into the BNST increased local NO release during restraint stress...
January 12, 2018: Psychoneuroendocrinology
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