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https://www.readbyqxmd.com/read/28527692/regional-differences-in-dopamine-receptor-blockade-affect-timing-impulsivity-that-are-altered-by-d-amphetamine-on-differential-reinforcement-of-low-rate-responding-drl-behavior-in-rats
#1
Ruey-Kuang Cheng, Ruey-Ming Liao
The ability to control when to start an action and when to stop is crucial in human and animal behavior. A failure to suppress premature behavior or carry out an action in a timely manner is commonly seen in several neuropsychological disorders. Despite the phenomenon, the exact neural mechanisms underlying this timing impulsivity remain to be elucidated. Systemic injection of d-amphetamine (AMP) has been shown to disrupt rat's performance in the differential reinforcement of low-rate (DRL) task that requires both optimal timing and proper impulsive control as measured by peak time and non-reinforced responses, respectively...
May 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#2
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28525574/a-schizophrenia-related-deletion-leads-to-kcnq2-dependent-abnormal-dopaminergic-modulation-of-prefrontal-cortical-interneuron-activity
#3
Se Joon Choi, Jun Mukai, Mirna Kvajo, Bin Xu, Anastasia Diamantopoulou, Pothitos M Pitychoutis, Bin Gou, Joseph A Gogos, Hui Zhang
Altered prefrontal cortex function is implicated in schizophrenia (SCZ) pathophysiology and could arise from imbalance between excitation and inhibition (E/I) in local circuits. It remains unclear whether and how such imbalances relate to genetic etiologies. We used a mouse model of the SCZ-predisposing 22q11.2 deletion (Df(16)A+/- mice) to evaluate how this genetic lesion affects the excitability of layer V prefrontal pyramidal neurons and its modulation by dopamine (DA). Df(16)A+/- mice have normal balance between E/I at baseline but are unable to maintain it upon dopaminergic challenge...
May 19, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28522735/d3-receptors-regulate-excitability-in-a-unique-class-of-prefrontal-pyramidal-cell
#4
Rebecca L Clarkson, Alayna T Liptak, Steven M Gee, Vikaas S Sohal, Kevin J Bender
The D3 dopamine receptor, a member of the Gi-coupled D2-family of dopamine receptors, is expressed throughout limbic circuits affected in neuropsychiatric disorders, including prefrontal cortex. These receptors are important for prefrontal executive function, as pharmacological and genetic manipulations that affect prefrontal D3 receptors alter anxiety, social interaction, and reversal learning. And yet, the mechanisms by which D3 receptors regulate prefrontal circuits, and whether D3 receptors regulate specific prefrontal subnetworks, remain unknown...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28522609/coagulation-factor-viia-mediated-protease-activated-receptor-2-activation-leads-to-%C3%AE-catenin-accumulation-via-the-akt-gsk3%C3%AE-pathway-and-contributes-to-breast-cancer-progression
#5
Abhishek Roy, Shabbir A Ansari, Kaushik Das, Ramesh Prasad, Anindita Bhattacharya, Suman Mallik, Asis Mukherjee, Prosenjit Sen
Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most vulnerable causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well-established that apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28520722/altered-detrusor-contractility-in-mptp-treated-common-marmosets-with-bladder-hyperreflexia
#6
Sara Pritchard, Michael J Jackson, Atsuko Hikima, Lisa Lione, Christopher D Benham, K Ray Chaudhuri, Sarah Rose, Peter Jenner, Mahmoud M Iravani
Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MPTP, the amplitude and frequency of spontaneous contraction was increased. These responses were unaffected by dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively. Contractions by exogenous carbachol, histamine or ATP were similar and no differences in the magnitude of noradrenaline-induced relaxation were seen in detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix jacchus)...
2017: PloS One
https://www.readbyqxmd.com/read/28514727/nuclear-receptor-nr4a1-is-a-tumor-suppressor-down-regulated-in-triple-negative-breast-cancer
#7
Hongmei Wu, Jiong Bi, Yan Peng, Lei Huo, Xiaobin Yu, Zhihui Yang, Yunyun Zhou, Li Qin, Yixiang Xu, Lan Liao, Yang Xie, Orla M Conneely, Jos Jonkers, Jianming Xu
The nuclear receptor (NR) superfamily contains hormone-inducible transcription factors that regulate many physiological and pathological processes through regulating gene expression. NR4A1 is an NR family member that still does not have an identified endogenous ligand, and its role in cancer is also currently unclear and controversial. In this study, we aimed to define the expression profiles and specific role of NR4A1 in the highly malignant triple-negative breast cancer (TNBC), which still lacks available targeted therapies...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28509598/elevated-dopamine-d1-receptor-availability-in-striatum-of-g%C3%A3-ttingen-minipigs-after-electroconvulsive-therapy
#8
Anne M Landau, Aage Ko Alstrup, Helene Audrain, Steen Jakobsen, Mette Simonsen, Arne Møller, Poul Videbech, Gregers Wegener, Albert Gjedde, Doris J Doudet
Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Göttingen minipigs based on the protocol of ECT applied in humans. With positron emission tomography (PET), we determined a measure of dopaminergic neurotransmission with the dopamine D1 receptor antagonist [(11)C]SCH23390...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28508842/a3-adenosine-receptor-agonist-induce-g1-cell-cycle-arrest-via-cyclin-d-and-cyclin-dependent-kinase-4-pathways-in-ovcar-3-and-caov-4-cell-lines
#9
Hamid Reza Joshaghani, Seyyed Mehdi Jafari, Mahmoud Aghaei, Mojtaba Panjehpour, Hamideh Abedi
AIM OF THE STUDY: The cell cycle, a vital process that involves in cells' growth and division, lies at the heart of cancer. It has been shown that IB-MECA, an A3 adenosine receptor agonist inhibits the proliferation of cancer cells by inducing cell cycle arrest in several tumors. In this study, we evaluated the role of IB-MECA inhibition in cell cycle progression in ovarian cancer cells. MATERIALS AND METHODS: Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in Caov-4 and OVCAR-3...
January 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28507800/formyl-peptide-receptor-1-suppresses-gastric-cancer-angiogenesis-and-growth-by-exploiting-inflammation-resolution-pathways
#10
Nella Prevete, Federica Liotti, Anna Illiano, Angela Amoresano, Piero Pucci, Amato de Paulis, Rosa Marina Melillo
Chronic inflammation can result from inadequate engagement of resolution mechanisms, mainly accomplished by specialized pro-resolving mediators (SPMs) arising from the metabolic activity of lipoxygenases (ALOX5/15) on ω-6 or ω-3 essential polyunsaturated fatty acids (PUFA). We previously demonstrated that formyl peptide receptor 1 (FPR1) suppresses gastric cancer (GC) by inhibiting its inflammatory/angiogenic potential. In this study, we asked whether FPR1 exploits inflammation resolution pathways to suppress GC angiogenesis and growth...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507136/ocd-candidate-gene-slc1a1-eaat3-impacts-basal-ganglia-mediated-activity-and-stereotypic-behavior
#11
Isaac D Zike, Muhammad O Chohan, Jared M Kopelman, Emily N Krasnow, Daniel Flicker, Katherine M Nautiyal, Michael Bubser, Christoph Kellendonk, Carrie K Jones, Gregg Stanwood, Kenji Fransis Tanaka, Holly Moore, Susanne E Ahmari, Jeremy Veenstra-VanderWeele
Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1, which encodes the neuronal glutamate/aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1)...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28502303/-effect-of-metformin-on-proliferation-and-apoptosis-of-rat-prolactinoma-mmq-cells-and-related-mechanisms
#12
Kai Jin, Lunliang Ruan, Jiujun Pu, Ailing Zhong, Fuchao Wang, Song Tan, Hua Huang, Jiamin Mou, Gang Yang
Objective To investigate the effect of metformin on the cell proliferation, cell cycle and apoptosis of rat prolactinoma MMQ cells in vitro and related molecular mechanisms. Methods The MMQ cells were treated with 1.25, 2.5, 5, 10, 20 mmol/L metformin for 48 hours. CCK-8 assay was used to assess the cell proliferation ability; flow cytometry was used to analyze the cell cycle distribution and apoptosis; Western blotting was performed to detect the expressions of AMPKα1/2, p-AMPKα, mTOR, p-mTOR, insulin like growth factor 1 receptor (IGF-1R), ERK1/2, p-ERK1/2, AKT, p-AKT, P21, CDK4, cyclin D1, caspase-3, cleaved caspase-3(c-caspase-3), Bcl-2 and BAX...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28499973/activation-of-dopamine-d1-receptors-enhances-the-temporal-summation-and-excitability-of-rat-retinal-ganglion-cells
#13
Peng Cui, Xue-Yan Li, Yuan Zhao, Qian Li, Feng Gao, Ling-Zhu Li, Ning Yin, Xing-Huai Sun, Zhongfeng Wang
Dopamine (DA), an important neurotransmitter and neuromodulator, plays important roles in neuronal physiological functions by activating G-protein-coupled DA D1 and/or D2 receptors. Previous studies have demonstrated that D1 receptors are functionally expressed in retinal neurons and glial cells, including ganglion cells. In this study, we explored the effects of D1 receptor activation on retinal ganglion cell (RGC) temporal summation and excitability in rat retinal slices using electrophysiological techniques...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28499899/the-wake-promoting-drug-modafinil-prevents-motor-impairment-in-sickness-behavior-induced-by-lps-in-mice-role-for-dopaminergic-d1-receptor
#14
Adriano Zager, Wesley Nogueira Brandão, Rafael Oliveira Margatho, Jean Pierre Peron, Sergio Tufik, Monica Levy Andersen, Birgitte Rahbek Kornum, João Palermo-Neto
The wake-promoting drug Modafinil has been used for many years for treatment of Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related psychostimulant action. Recent studies have indicated that Modafinil prevents neuroinflammation in animal models. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced sickness and depressive-like behaviors. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil (90mg/Kg) and, 30min later, received a single saline or LPS (2mg/Kg) administration, and were submitted to the open field and elevated plus maze test 2h later...
May 9, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28497372/scara5-plays-a-critical-role-in-the-progression-and-metastasis-of-breast-cancer-by-inactivating-the-erk1-2-stat3-and-akt-signaling-pathways
#15
Kai You, Fei Su, Lihua Liu, Xiaohong Lv, Jianguo Zhang, Yafang Zhang, Baoquan Liu
Scavenger receptor class A member 5 (SCARA5) is a candidate anti-oncogene in several malignancies. However, whether SCARA5 is a suppressor gene in breast cancer and its role in breast cancer cell growth and metastasis remain to be determined. Here, we investigated the biological functions of SCARA5 in the progression and metastasis of breast cancer and explored the underlying mechanisms. A total of 65 breast cancer patients and three cell lines (ZR-75-30, MCF-7, and MDA-MB-231) were analyzed in the study. RT-qPCR, western blotting, and immunohistochemistry were used to detect mRNA and protein expression, and lymphatic vessel density (LVD) and microvessel density (MVD)...
May 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28495611/hiv-1-tat-protein-enhances-sensitization-to-methamphetamine-by-affecting-dopaminergic-function
#16
James P Kesby, Julia A Najera, Benedetto Romoli, Yiding Fang, Liana Basova, Amanda Birmingham, Maria Cecilia G Marcondes, Davide Dulcis, Svetlana Semenova
Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period...
May 8, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28495607/prenatal-exposure-to-lambda-cyhalothrin-alters-brain-dopaminegric-signalling-in-developing-rats
#17
Yogesh K Dhuriya, Pranay Srivastava, Rajendra K Shukla, Richa Gupta, Dhirendra Singh, Devendra Parmar, Aditya B Pant, Vinay K Khanna
The present study is focused to decipher the molecular mechanisms associated with dopaminergic alterations in corpus striatum of developing rats exposed prenatally to lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid. There was no significant change in the mRNA and protein expression of DA-D1 receptors at any of the doses of LCT (0.5, 1 & 3mg/kg body weight) in corpus striatum of developing rats exposed prenatally to LCT on PD22 & PD45. Prenatal exposure to LCT (1 & 3mg/kg body weight) resulted to decrease the level of mRNA and protein of DA-D2 receptors in corpus stratum of developing rats on PD22 as compared to controls...
May 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28493981/within-session-decrement-of-the-emission-of-licking-bursts-following-reward-devaluation-in-rats-licking-for-sucrose
#18
Paolo S D'Aquila, Adriana Galistu
We previously observed that dopamine D2-like receptor blockade in rats licking for sucrose produced a within-session decrement of the emission of licking bursts similar to the effect of either reward devaluation, or neuroleptics, on operant responding for different rewards, which, accordingly, we interpreted as an extinction-like effect. This implies that exposing animals to reward devaluation would result in a drop of burst number taking place only after the contact with the devalued reward. To test this prediction, we compared the difference in the within-session time course of burst number in response to high (10%) versus low (2%) concentration sucrose solutions, either in a condition of reward devaluation (exposure to 2% after daily 10%), or in a condition which does not involve changes in the reward value (two groups of subjects each repeatedly exposed to only one of the two concentrations)...
2017: PloS One
https://www.readbyqxmd.com/read/28490442/dexamethasone-and-sex-regulate-placental-glucocorticoid-receptor-isoforms-in-mice
#19
James Sm Cuffe, Zarqa Saif, Anthony V Perkins, Karen M Moritz, Vicki L Clifton
Maternal dexamethasone exposure in the mouse impairs placental development and programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to different glucocorticoid receptor (GR) isoforms to regulate gene transcription and cellular signaling. We hypothesized that sexually dimorphic placental responses to glucocorticoids are due to differences in GR isoforms present in the placenta. Pregnant C57Bl6 mice were exposed to saline or dexamethasone from E12.5 until E14.5 (1µg/kg/h) before the collection of placentae...
May 10, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28489950/the-return-of-d4-dopamine-receptor-antagonists-in-drug-discovery
#20
Craig W Lindsley, Corey R Hopkins
The dopamine D4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D4, relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Coupled with genetic association of the DRD4 gene with various CNS disorders, multiple companies launched discovery programs to develop selective D4 antagonists. Merck's D4 antagonist L-745,870 was the first to reach the clinic, where it was found to be ineffective in schizophrenia patients, and other groups failed to recapitulate some of the genetic data...
May 10, 2017: Journal of Medicinal Chemistry
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