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new neural receptor sites

Anja Probst Larsen, Sabine Fievre, Karla Frydenvang, Pierre Francotte, Bernard Pirotte, Jette Sandholm Karstrup, Christophe Mulle
Kainate receptors (KARs) consist of a class of ionotropic glutamate receptors, which exert diverse pre- and postsynaptic functions through complex signaling regulating the activity of neural circuits. Whereas numerous small-molecule positive allosteric modulators of the ligand-binding domain of AMPA receptors have been reported, no such ligands are available for KARs. In this study, we have investigated the ability of three benzothiadiazine-based modulators to potentiate glutamate-evoked currents at recombinantly expressed KARs...
March 30, 2017: Molecular Pharmacology
Joseph A McQuail, B Sofia Beas, Kyle B Kelly, Kailey L Simpson, Charles J Frazier, Barry Setlow, Jennifer L Bizon
Working memory, the ability to temporarily maintain representational knowledge, is a foundational cognitive process that can become compromised in aging and neuropsychiatric disease. NMDA receptor (NMDAR) activation in prefrontal cortex (PFC) is necessary for the pyramidal neuron activity believed to enable working memory; however, the distinct biophysical properties and localization of NMDARs containing NR2A and NR2B subunits suggest unique roles for NMDAR subtypes in PFC neural activity and working memory...
December 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Bi-Qin Lai, Ming-Tian Che, Bao-Ling Du, Xiang Zeng, Yuan-Huan Ma, Bo Feng, Xue-Chen Qiu, Ke Zhang, Shu Liu, Hui-Yong Shen, Jin-Lang Wu, Eng-Ang Ling, Yuan-Shan Zeng
Severe spinal cord injury (SCI) causes loss of neural connectivity and permanent functional deficits. Re-establishment of new neuronal relay circuits after SCI is therefore of paramount importance. The present study tested our hypothesis if co-culture of neurotrophin-3 (NT-3) gene-modified Schwann cells (SCs, NT-3-SCs) and TrkC (NT-3 receptor) gene-modified neural stem cells (NSCs, TrkC-NSCs) in a gelatin sponge scaffold could construct a tissue engineering neural network for re-establishing an anatomical neuronal relay after rat spinal cord transection...
December 2016: Biomaterials
Heather Kang, Pojeong Park, Zuner A Bortolotto, Simon D Brandt, Tristan Colestock, Jason Wallach, Graham L Collingridge, David Lodge
To avoid legislation based on chemical structure, research chemicals, frequently used for recreational purposes, are continually being synthesized. N-Ethyl-1,2-diphenylethanamine (ephenidine) is a diarylethylamine that has recently become popular with recreational users searching for dissociative hallucinogenic effects. In the present study, the pharmacological basis of its neural actions has been investigated, initially by assessing its profile in central nervous system receptor binding assays and subsequently in targeted electrophysiological studies...
January 2017: Neuropharmacology
S Sisó, P Marco-Salazar, P F Moore, B K Sturges, W Vernau, E R Wisner, A W Bollen, P J Dickinson, R J Higgins
Primary and secondary nervous system involvement occurs in 4% and 5%-12%, respectively, of all canine non-Hodgkin lymphomas. The recent new classification of canine malignant lymphomas, based on the human World Health Organization classification, has been endorsed with international acceptance. This histological and immunocytochemical classification provides a unique opportunity to study the histologic anatomic distribution patterns in the central and peripheral nervous system of these defined lymphoma subtypes...
January 2017: Veterinary Pathology
Sangho Yu, Emily Qualls-Creekmore, Kavon Rezai-Zadeh, Yanyan Jiang, Hans-Rudolf Berthoud, Christopher D Morrison, Andrei V Derbenev, Andrea Zsombok, Heike Münzberg
UNLABELLED: The preoptic area (POA) regulates body temperature, but is not considered a site for body weight control. A subpopulation of POA neurons express leptin receptors (LepRb(POA) neurons) and modulate reproductive function. However, LepRb(POA) neurons project to sympathetic premotor neurons that control brown adipose tissue (BAT) thermogenesis, suggesting an additional role in energy homeostasis and body weight regulation. We determined the role of LepRb(POA) neurons in energy homeostasis using cre-dependent viral vectors to selectively activate these neurons and analyzed functional outcomes in mice...
May 4, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
George R Breese, Darin J Knapp
This review updates the conceptual basis for the association of alcohol abuse with an insidious adaptation that facilitates negative affect during withdrawal from chronic intermittent alcohol (CIA) exposure - a change that later supports sensitization of stress-induced anxiety following alcohol abstinence. The finding that a CRF1-receptor antagonist (CRF1RA) minimized CIA withdrawal-induced negative affect supported an association of alcohol withdrawal with a stress mechanism. The finding that repeated stresses or multiple CRF injections into selected brain sites prior to a single 5-day chronic alcohol (CA) exposure induced anxiety during withdrawal provided critical support for a linkage of CIA withdrawal with stress...
May 2016: Alcohol
Yu-Jun Wang, Ai Hang, Yu-Chen Lu, Yu Long, Gui-Ying Zan, Xue-Ping Li, Qian Wang, Zeng-Xiang Zhao, Ling He, Zhi-Qiang Chi, Jing-Gen Liu
κ Opioid receptor system is widely implicated in the regulation of emotion. However, the findings about the role on anxiety in rodents are highly controversial, since both anxiogenic- and anxiolytic-like effects have been reported with κ opioid receptor activation. The mechanism and the underlying neuroanatomical substrates are unexplored. In the present study, we first investigated the effects of κ agonist U50,488H on anxiety-related behaviors over a wide range of doses, and we found that U50,488H produced dual effects in anxiety, with low dose being anxiogenic and high dose being anxiolytic...
November 2016: Neuropharmacology
Jorge Eduardo Shortrede, Ivonne Denise Uzair, Flavia Judith Neira, Marina Inés Flamini, Angel Matías Sanchez
Breast cancer is the major cause of cancer-related death in women. Its treatment is particularly difficult when metastasis occurs. The ability of cancer cells to move and invade the surrounding environment is the basis of local and distant metastasis. Cancer cells are able to remodel the actin cytoskeleton, which requires the recruitment of numerous structural and regulatory proteins that modulate actin filaments dynamics, including Paxillin or the Neural Wiskott-Aldrich Syndrome Protein (N-WASP). We show that 17-β estradiol (E2) induces phosphorylation of Paxillin and its translocation toward membrane sites where focal adhesion complexes are assembled...
July 15, 2016: Molecular and Cellular Endocrinology
Sara M Freeman, Larry J Young
In the last several decades, sophisticated experimental techniques have been used to determine the neurobiology of the oxytocin and vasopressin systems in rodents. Using a suite of methodologies, including electrophysiology, site-specific selective pharmacology, receptor autoradiography, in vivo microdialysis, and genetic and optogenetic manipulations, we have gained unprecedented knowledge about how these neuropeptides engage neural circuits to regulate behaviour, particularly social behaviour. Based on this foundation of information from rodent studies, we have started generating new hypotheses and frameworks about how the oxytocin and vasopressin systems could be acting in humans to influence social cognition...
April 2016: Journal of Neuroendocrinology
Michael R Koelle
Neurotransmitters signal via G protein coupled receptors (GPCRs) to modulate activity of neurons and muscles. C. elegans has ~150 G protein coupled neuropeptide receptor homologs and 28 additional GPCRs for small-molecule neurotransmitters. Genetic studies in C. elegans demonstrate that neurotransmitters diffuse far from their release sites to activate GPCRs on distant cells. Individual receptor types are expressed on limited numbers of cells and thus can provide very specific regulation of an individual neural circuit and behavior...
March 3, 2016: WormBook: the Online Review of C. Elegans Biology
Owen Y Chao, Joseph P Huston, Susanne Nikolaus, Maria A de Souza Silva
We here explore the utility of a paradigm that allows the simultaneous assessment of memory for object (what) and object location (where) and their comparative predominance. Two identical objects are presented during a familiarity trial; during the test trial one of these is displaced, and a new object is presented in a familiar location. When tested 5 or 80min later, rats explored both the novel and the displaced objects more than two familiar stationary objects, indicating intact memory for both, object and place...
April 2016: Neurobiology of Learning and Memory
Emilio Sacco, Riccardo Bientinesi, Pierfrancesco Bassi, Diego Currò
INTRODUCTION: Licenced oral pharmacotherapies for overactive bladder (OAB) act on muscarinic receptors or β3-adrenoceptors. The search for new drugs to treat OAB that have novel mechanisms of action is very active, with the aim of discovering more effective and/or better tolerated agents. METHODS: A literature review of the most frequently used pharmacological methods for the preclinical assessment of new agents aimed at treating OAB, such as isolated organ technique, electrophysiological techniques, radioligand binding assay, and animal models, was carried out...
November 2016: International Urogynecology Journal
Miyako Takaki, Kei Goto, Isao Kawahara, Junich Nabekura
Two-photon microscopy (2PM) can enable high-resolution deep imaging of thick tissue by exciting a fluorescent dye and protein at anastomotic sites in the mouse small intestine in vivo. We performed gut surgery and transplanted neural stem cells (NSC) from the embryonic central nervous system after marking them with the fluorescent cell linker, PKH26. We found that neurons differentiated from transplanted NSC (PKH [+]) and newborn enteric neurons differentiated from mobilized (host) NSC (YFP [+]) could be localized within the granulation tissue of anastomoses...
2015: Journal of Smooth Muscle Research, Nihon Heikatsukin Gakkai Kikanshi
Fatma Aksakal, Natali Shvets, Veronika Khairullina, Anatholy Dimoglo
Structural and electronic factors influencing the inhibition of cyclooxygenase-1 and -2 (COX-1/COX-2) were studied by means of Electronic-Topological Method combined with Neural Networks (ETM-NN), molecular docking and Density Functional Theory (DFT). A series of structurally diverse compounds containing 209 molecules were classified in accordance with their inhibiting properties, as selectively inhibiting and non-selectively inhibiting COX-2 receptor agents (110 and 99 molecules, correspondingly). The results obtained from the ETM-NN calculations gave us possibility of selecting those pharmacophoric molecular fragments, which allow for the search of new selective inhibitors of COX-2 with high probability of realization...
2016: Mini Reviews in Medicinal Chemistry
Ivar S Stein, John A Gray, Karen Zito
UNLABELLED: The elimination of dendritic spine synapses is a critical step in the refinement of neuronal circuits during development of the cerebral cortex. Several studies have shown that activity-induced shrinkage and retraction of dendritic spines depend on activation of the NMDA-type glutamate receptor (NMDAR), which leads to influx of extracellular calcium ions and activation of calcium-dependent phosphatases that modify regulators of the spine cytoskeleton, suggesting that influx of extracellular calcium ions drives spine shrinkage...
September 2, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Gisela Garcia-Alvarez, Mahesh S Shetty, Bo Lu, Kenrick An Fu Yap, Masatsugu Oh-Hora, Sreedharan Sajikumar, Zoë Bichler, Marc Fivaz
Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping the structure and function of excitatory synapses in the mammalian brain. The impact of the Stim genes on cognitive functions remains, however, poorly understood. To explore the function of the Stim genes in learning and memory, we generated three mouse strains with conditional deletion (cKO) of Stim1 and/or Stim2 in the forebrain. Stim1, Stim2, and double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor impairment...
2015: Frontiers in Behavioral Neuroscience
Jean-François Schmouth, David Arenillas, Ximena Corso-Díaz, Yuan-Yun Xie, Slavita Bohacec, Kathleen G Banks, Russell J Bonaguro, Siaw H Wong, Steven J M Jones, Marco A Marra, Elizabeth M Simpson, Wyeth W Wasserman
BACKGROUND: Nr2e1 (nuclear receptor subfamily 2, group e, member 1) encodes a transcription factor important in neocortex development. Previous work has shown that nuclear receptors can have hundreds of target genes, and bind more than 300 co-interacting proteins. However, recognition of the critical role of Nr2e1 in neural stem cells and neocortex development is relatively recent, thus the molecular mechanisms involved for this nuclear receptor are only beginning to be understood. Serial analysis of gene expression (SAGE), has given researchers both qualitative and quantitative information pertaining to biological processes...
2015: BMC Genomics
Christopher S Walker, Sajedeh Eftekhari, Rebekah L Bower, Andrea Wilderman, Paul A Insel, Lars Edvinsson, Henry J Waldvogel, Muhammad A Jamaluddin, Andrew F Russo, Debbie L Hay
OBJECTIVE: The trigeminovascular system plays a central role in migraine, a condition in need of new treatments. The neuropeptide, calcitonin gene-related peptide (CGRP), is proposed as causative in migraine and is the subject of intensive drug discovery efforts. This study explores the expression and functionality of two CGRP receptor candidates in the sensory trigeminal system. METHODS: Receptor expression was determined using Taqman G protein-coupled receptor arrays and immunohistochemistry in trigeminal ganglia (TG) and the spinal trigeminal complex of the brainstem in rat and human...
June 2015: Annals of Clinical and Translational Neurology
ZaWaunyka W Lazard, Elizabeth A Olmsted-Davis, Elizabeth A Salisbury, Zbigniew Gugala, Corrine Sonnet, Eleanor L Davis, Eric Beal, Eroboghene E Ubogu, Alan R Davis
BACKGROUND: Heterotopic ossification (HO) is the process of bone formation at a nonskeletal site. Recently, we showed that the earliest steps occur in sensory nerves. We now extend these studies by identifying unique osteogenic progenitors within the endoneurial compartment of sensory nerves. QUESTIONS/PURPOSES: We asked: (1) What is the nature of the osteoprogenitor in the endoneurium of peripheral nerves? (2) How do osteoprogenitors travel from the nerve to the site of new bone formation? METHODS: HO was induced by intramuscular injection of Ad5BMP-2-transduced cells in mice...
September 2015: Clinical Orthopaedics and related Research
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