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https://www.readbyqxmd.com/read/28228586/modeling-the-diversity-of-spontaneous-and-agonist-induced-electrical-activity-in-anterior-pituitary-corticotrophs
#1
Patrick Allen Fletcher, Hana Zemkova, Stanko S Stojilkovic, Arthur Sherman
Pituitary corticotrophs fire action potentials spontaneously and in response to stimulation with corticotropin-releasing hormone (CRH) and arginine vaspressin (AVP), and such electrical activity is critical for calcium signaling and calcium-dependent adrenocorticotropic hormone (ACTH) secretion. These cells typically fire tall sharp action potentials when spontaneously active, but a variety of other spontaneous patterns have also been reported, including various modes of bursting. There is variability in reports of the fraction of corticotrophs that are electrically active, as well as their patterns of activity, and the sources of this variation are not well understood...
February 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28228090/cardioprotective-utility-of-urocortin-in-myocardial-ischemia-reperfusion-injury-where-do-we-stand
#2
Craig Basman, Pratik Agrawal, Richard Knight, Louis Saravolatz, Chad McRee, Carol Chen-Scarabelli, Jagat Narula, Tiziano Scarabelli
There has been a constant pursuit for development of newer therapies which can contribute to the relatively nascent field of cardioprotection in the setting of myocardial ischemia-reperfusion injury. One novel cardioprotective agent among others, that has shown promising results in the limited number of research studies undertaken till now, is Urocortin. Urocortins are peptides belonging to the Corticotropin-Releasing Hormone family. Acting through a variety of downstream mechanisms, urocortin has been shown to alter cellular metabolism and modulate the mechanism of cell death occurring as a result of ischemia-reperfusion injury...
February 22, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28223925/effects-of-intermittent-alcohol-exposure-on-emotion-and-cognition-a-potential-role-for-the-endogenous-cannabinoid-system-and-neuroinflammation
#3
Laura Sanchez-Marin, Francisco J Pavon, Juan Decara, Juan Suarez, Ana Gavito, Estela Castilla-Ortega, Fernando Rodriguez de Fonseca, Antonia Serrano
Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28223020/synthesis-and-evaluation-of-prodrugs-of-corticotropin-releasing-factor-1-crf1-receptor-antagonist-bms-665053-leading-to-improved-oral-bioavailability
#4
Richard A Hartz, Vivekananda M Vrudhula, Vijay T Ahuja, James E Grace, Nicholas J Lodge, Joanne J Bronson, John E Macor
A series of phosphate and ester-based prodrugs of anilinopyrazinone 1 (BMS-665053) containing either a methylene or an (acyloxy)alkoxy linker was prepared and evaluated in rat pharmacokinetic studies with the goal of improving the oral bioavailability of the parent (1). The prodrugs, in general, had improved aqueous solubility and oral bioavailability compared to 1. Prodrug 12, which contains an (acyloxy)alkoxy linker, showed the greatest improvement in the oral bioavailability relative to the parent (1), with a seven-fold increase (from 5% to 36%) in rat pharmacokinetic studies...
February 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28222901/pharmacotherapy-in-smoking-cessation-corticotropin-releasing-factor-receptors-as-emerging-intervention-targets
#5
REVIEW
Ioannis Sotiriou, Kleanthi Chalkiadaki, Christos Nikolaidis, Kyriaki Sidiropoulou, Ekaterini Chatzaki
Smoking represents perhaps the single most important health risk factor and a global contributor to mortality that can unquestionably be prevented. Smoking is responsible for many diseases, including various types of cancer, chronic obstructive pulmonary disease, coronary heart disease, peripheral vascular disease and peptic ulcer, while it adversely affects fetal formation and development. Since smoking habit duration is a critical factor for mortality, the goal of treatment should be its timely cessation and relapse prevention...
February 14, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28220796/beyond-the-classic-vta-extended-amygdala-projections-to-da-striatal-paths-in-the-primate
#6
Julie L Fudge, Emily A Kelly, Ria Pal, Joseph L Bedont, Lydia Park, Brian Ho
The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways...
February 21, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28209423/constitutive-increases-in-amygdalar-corticotropin-releasing-factor-and-fatty-acid-amide-hydrolase-drive-an-anxious-phenotype
#7
Luis A Natividad, Matthew W Buczynski, Melissa A Herman, Dean Kirson, Christopher S Oleata, Cristina Irimia, Ilham Polis, Roberto Ciccocioppo, Marisa Roberto, Loren H Parsons
BACKGROUND: Corticotropin-releasing factor (CRF) mediates anxiogenic responses by activating CRF type 1 (CRF1) receptors in limbic brain regions. Anxiety is further modulated by the endogenous cannabinoid (eCB) system that attenuates the synaptic effects of stress. In the amygdala, acute stress activates the enzymatic clearance of the eCB N-arachidonoylethanolamine via fatty acid amide hydrolase (FAAH), although it is unclear whether chronic dysregulation of CRF systems induces maladaptive changes in amygdalar eCB signaling...
January 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28202248/possible-role-of-adrenoceptors-in-the-hypothalamic-paraventricular-nucleus-in-corticotropin-releasing-factor-induced-sympatho-adrenomedullary-outflow-in-rats
#8
Shoshiro Okada, Naoko Yamaguchi
AIMS: A functional interaction between the corticotropin-releasing factor (CRF) system and noradrenergic neurons in the brain has been suggested. In the present study, we investigated the interrelationship between the central CRF-induced elevation of plasma catecholamines and adrenoceptor activation in the paraventricular nucleus of the hypothalamus (PVN) using urethane-anesthetized rats. MAIN METHODS: In rats under urethane anesthesia, a femoral venous line was inserted for infusion of saline, and a femoral arterial line was inserted for collecting blood samples...
February 9, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28189027/the-flame-retardant-2-2-4-4-tetrabromodiphenyl-ether-enhances-the-expression-of-corticotropin-releasing-hormone-in-the-placental-cell-model-jeg-3
#9
Yun Zhu, Yan Qin Tan, Chi Chiu Wang, Lai K Leung
Polybrominated diphenyl ethers (PBDEs) are chemicals used as flame retardants in household products. After disposing of these items, PBDEs leach from the products by surface water. BDE-47 is a PBDE congener commonly isolated from contaminated food and is the most studied isomer. The placenta is the major source of hormones during pregnancy, and an elevated level of corticotrophin-releasing hormone (CRH) is associated with premature delivery. In the present study, we examined changes in the placental CRH expression under BDE-47 exposure in the JEG-3 cell model system...
January 31, 2017: Chemosphere
https://www.readbyqxmd.com/read/28185482/suckling-induced-activation-pattern-in-the-brain-of-rat-pups
#10
János Barna, Eva Renner, Antónia Arszovszki, Melinda Cservenák, Zsolt Kovács, Miklós Palkovits, Arpád Dobolyi
OBJECTIVES: The aim of the study was to understand the effects of suckling on the brain of the pups by mapping their brain activation pattern in response to suckling. METHODS: The c-fos method was applied to identify activated neurons. Fasted rat pups were returned to their mothers for suckling and sacrificed 2 hours later for Fos immunohistochemistry. Double labeling was also performed to characterize some of the activated neurons. For comparison, another group of fasted pups were given dry food before Fos mapping...
February 10, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28183242/decoding-corticotropin-releasing-factor-receptor-type-1-crystal-structures
#11
Andrew S Doré, Andrea Bortolato, Kaspar Hollenstein, Robert K Y Cheng, Randy J Read, Fiona H Marshall
The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Corticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28179810/sex-biased-cellular-signaling-molecular-basis-for-sex-differences-in-neuropsychiatric-diseases
#12
Rita J Valentino, Debra A Bangasser
The recognition that there are fundamental biological sex differences that extend beyond those that define sexual behavior and reproductive function has inspired the drive toward inclusion of both sexes in research design. This is supported by an underlying clinical rationale that studying both sexes is necessary to elucidate pathophysiology and develop treatments for the entire population. However, at a more basic level, sex differences, like genetic differences, can be exploited to better understand biology...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28174066/discovery-of-4-chloro-2-2-4-dichloro-6-methylphenoxy-1-methyl-7-pentan-3-yl-1h-benzimidazole-a-novel-crf1-receptor-antagonist
#13
Michiyo Mochizuki, Takuto Kojima, Katsumi Kobayashi, Etsuo Kotani, Yuji Ishichi, Naoyuki Kanzaki, Hideyuki Nakagawa, Teruaki Okuda, Yohei Kosugi, Takahiko Yano, Yuu Sako, Maiko Tanaka, Kazuyoshi Aso
Compound 1 exhibits potent binding inhibition activity against a corticotropin-releasing factor 1 (CRF1) receptor (IC50=9.5nM) and in vitro antagonistic activity (IC50=88nM) but is rapidly metabolized by human hepatic microsomes (182μL/min/mg). Here we identified metabolically stable compounds with potent CRF binding inhibitory activity. Structure-activity relationship (SAR) studies considering in vitro metabolic stability revealed that 4-chloro-2-(2,4-dichloro-6-methylphenoxy)-1-methyl-7-(pentan-3-yl)-1H-benzimidazole 24d was more stable in human microsomes (87μL/min/mg) than compound 1...
November 8, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28170426/chronic-social-stress-in-pigs-impairs-intestinal-barrier-and-nutrient-transporter-function-and-alters-neuro-immune-mediator-and-receptor-expression
#14
Yihang Li, Zehe Song, Katelyn A Kerr, Adam J Moeser
Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0...
2017: PloS One
https://www.readbyqxmd.com/read/28167808/how-do-individuals-cope-with-stress-behavioural-physiological-and-neuronal-differences-between-proactive-and-reactive-coping-styles-in-fish
#15
Marco A Vindas, Marnix Gorissen, Erik Höglund, Gert Flik, Valentina Tronci, Børge Damsgård, Per-Ove Thörnqvist, Tom O Nilsen, Svante Winberg, Øyvind Øverli, Lars O E Ebbesson
Despite the use of fish models to study human mental disorders and dysfunctions, knowledge of regional telencephalic responses in non-mammalian vertebrates expressing alternate stress coping styles is poor. Since perception of salient stimuli associated with stress coping in mammals is mainly under forebrain limbic control, we tested region-specific forebrain neural (i.e mRNA abundance and monoamine neurochemistry) and endocrine responses at basal and acute stress conditions for previously characterised proactive and reactive Atlantic salmon...
February 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28164167/neonatal-maternal-separation-increases-susceptibility-to-experimental-colitis-and-acute-stress-exposure-in-male-mice
#16
Isabella M Fuentes, Natalie K Walker, Angela N Pierce, Briana R Holt, Elizabeth R Di Silvestro, Julie A Christianson
Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS) would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1-21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR) to colorectal distension (CRD)...
December 2016: IBRO Rep
https://www.readbyqxmd.com/read/28162848/altered-functionality-of-the-corticotrophin-releasing-hormone-receptor-2-in-the-hypothalamic-paraventricular-nucleus-of-hyperphagic-maternally-separated-rats
#17
V Alcántara-Alonso, M I Amaya, G Matamoros-Trejo, P de Gortari
Early-life stress induces endocrine and metabolic alterations that increase food intake and overweight in adulthood. The stress response activates the corticotropin-releasing hormone (CRH) and urocortins' (Ucns) system in the hypothalamic paraventricular nucleus (PVN). These peptides induce anorexic effects through CRH-R2 receptor activation; however, chronic stressed animals develop hyperphagia despite of high PVN CRH expression. We analyzed this paradoxical behavior in adult rats subjected to maternal separation (MS) for 180min/daily during post-natal days 2-14, evaluating their body weight gain, food intake, serum corticosterone and vasopressin concentrations, PVN mRNA expression of CRH-R1, CRH-R2, CRH, Ucn2, Ucn3, vasopressin and CRH-R2 protein levels...
February 1, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28151936/promoter-methylation-pattern-controls-corticotropin-releasing-hormone-gene-activity-in-human-trophoblasts
#18
Xin Pan, Maria Bowman, Rodney J Scott, John Fitter, Roger Smith, Tamas Zakar
Placental CRH production increases with advancing pregnancy in women and its course predicts gestational length. We hypothesized that CRH gene expression in the placenta is epigenetically controlled setting gestational trajectories characteristic of normal and pathological pregnancies. Here we determined histone modification and DNA methylation levels and DNA methylation patterns at the CRH promoter in primary trophoblast cultures by chromatin immunoprecipitation combined with clonal bisulfite sequencing and identified the transcriptionally active epialleles that associate with particular histone modifications and transcription factors during syncytialisation and cAMP-stimulation...
2017: PloS One
https://www.readbyqxmd.com/read/28140406/control-of-chronic-excessive-alcohol-drinking-by-genetic-manipulation-of-the-edinger-westphal-nucleus-urocortin-1-neuropeptide-system
#19
W J Giardino, E D Rodriguez, M L Smith, M M Ford, D Galili, S H Mitchell, A Chen, A E Ryabinin
Midbrain neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) are activated by alcohol, and enriched with stress-responsive neuropeptide modulators (including the paralog of corticotropin-releasing factor, urocortin-1). Evidence suggests that EWcp neurons promote behavioral processes for alcohol-seeking and consumption, but a definitive role for these cells remains elusive. Here we combined targeted viral manipulations and gene array profiling of EWcp neurons with mass behavioral phenotyping in C57BL/6 J mice to directly define the links between EWcp-specific urocortin-1 expression and voluntary binge alcohol intake, demonstrating a specific importance for EWcp urocortin-1 activity in escalation of alcohol intake...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28137650/functional-evidence-that-the-nucleus-of-the-hippocampal-commissure-shows-an-earlier-activation-from-a-stressor-than-the-paraventricular-nucleus-implication-of-an-additional-structural-component-of-the-avian-hypothalamo-pituitary-adrenal-axis
#20
Gurueswar Nagarajan, Seong W Kang, Wayne J Kuenzel
Despite extensive data addressing the regulation of the hypothalamo-pituitary-adrenal (HPA) axis in vertebrates, the neuroendocrine regulation of stress in birds remains incomplete. The paraventricular nucleus (PVN) contains the key neuropeptides, corticotropin releasing hormone (CRH) and arginine vasotocin (AVT), containing neurons. However, another population of CRH neurons was recently identified in a septal nucleus called the nucleus of the hippocampal commissure (NHpC). Therefore, the current study investigated changes in gene expression of CRH and AVT in the PVN and CRH in the NHpC, as well as changes in plasma corticosterone concentrations following a stressor, food deprivation...
January 27, 2017: Neuroscience Letters
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