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newly discovered neural receptors

Shih-Ching Lo, Yuanyuan Wang, Martin Weber, Jessica L Larson, Kimberly Scearce-Levie, Morgan Sheng
The ability to attend to relevant stimuli and to adapt dynamically as demands change is a core aspect of cognition, and one that is impaired in several neuropsychiatric diseases, including attention deficit/hyperactivity disorder. However, the cellular and molecular mechanisms underlying such cognitive adaptability are poorly understood. We found that deletion of the caspase-3 gene, encoding an apoptosis protease with newly discovered roles in neural plasticity, disrupts attention in mice while preserving multiple learning and memory capabilities...
February 4, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Bingjie Han, Andrew Bellemer, Michael R Koelle
The neurotransmitter gamma-aminobutyric acid (GABA) is depolarizing in the developing vertebrate brain, but in older animals switches to hyperpolarizing and becomes the major inhibitory neurotransmitter in adults. We discovered a similar developmental switch in GABA response in Caenorhabditis elegans and have genetically analyzed its mechanism and function in a well-defined circuit. Worm GABA neurons innervate body wall muscles to control locomotion. Activation of GABAA receptors with their agonist muscimol in newly hatched first larval (L1) stage animals excites muscle contraction and thus is depolarizing...
April 2015: Genetics
Craig M Smith, Andrew W Walker, Ihaia T Hosken, Berenice E Chua, Cary Zhang, Mouna Haidar, Andrew L Gundlach
Animal and clinical studies of gene-environment interactions have helped elucidate the mechanisms involved in the pathophysiology of several mental illnesses including anxiety, depression, and schizophrenia; and have led to the discovery of improved treatments. The study of neuropeptides and their receptors is a parallel frontier of neuropsychopharmacology research and has revealed the involvement of several peptide systems in mental illnesses and identified novel targets for their treatment. Relaxin-3 is a newly discovered neuropeptide that binds, and activates the G-protein coupled receptor, RXFP3...
2014: Frontiers in Pharmacology
Charles S Berenson, Hesham F Nawar, Ragina L Kruzel, Lorrie M Mandell, Terry D Connell
Bacterial heat-labile (LT) enterotoxins signal through tightly regulated interactions with host cell gangliosides. LT-IIa and LT-IIb of Escherichia coli bind preferentially to gangliosides with a NeuAcα2-3Galβ1-3GalNAc terminus, with key distinctions in specificity. LT-IIc, a newly discovered E. coli LT, is comprised of an A polypeptide with high homology, and a B polypeptide with moderate homology, to LT-IIa and LT-IIb. LT-IIc is less cytotoxic than LT-IIa and LT-IIb. We theorized that LT-IIc-host cell interaction is regulated by specific structural attributes of immune cell ganglioside receptors and designed experiments to test this hypothesis...
January 2013: Glycobiology
Despina E Ganella, Philip J Ryan, Ross A D Bathgate, Andrew L Gundlach
This paper provides a review of the effects of relaxin-3 and structurally related analogues on food intake and related behaviours, in relation to hypothalamic neural networks and chemical messengers known to control feeding, metabolism and body weight, including other neuropeptides and hormones. Soon after relaxin-3 was discovered, pharmacological studies identified the ability of the native peptide to stimulate feeding acutely in adult rats. Although interpretation of these data was confounded by ligand cross-reactivity at relaxin-family peptide (RXFP) receptors, studies with relaxin-3 analogues selective for the native relaxin-3 receptor, RXFP3, confirmed that acute and chronic activation of RXFP3 increased feeding and weight gain, and produced changes in plasma leptin and insulin...
September 2012: Behavioural Pharmacology
Jiang Qian, Ling Zhu, Qiming Li, Natalya Belevych, Qun Chen, Fangli Zhao, Scott Herness, Ning Quan
Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accessory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1-induced effects. Several recent studies, however, suggest the existence of a heretofore-unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter that drives the transcription of a shortened IL-1R1 mRNA...
July 24, 2012: Proceedings of the National Academy of Sciences of the United States of America
Yao-Qi Wang, Long Wang, Ming-Yang Zhang, Tao Wang, Hai-Jun Bao, Wei-Li Liu, Ding-Kun Dai, Lu Zhang, Pan Chang, Wen-Wen Dong, Xi-Ping Chen, Lu-Yang Tao
Traumatic brain injury (TBI) results in neuronal apoptosis, autophagic cell death and necroptosis. Necroptosis is a newly discovered caspases-independent programmed necrosis pathway which can be triggered by activation of death receptor. Previous works identified that necrostatin-1 (NEC-1), a specific necroptosis inhibitor, could reduce tissue damage and functional impairment through inhibiting of necroptosis process following TBI. However, the role of NEC-1 on apoptosis and autophagy after TBI is still not very clear...
September 2012: Neurochemical Research
Jeffrey S Diamond
The retina transforms light entering the eye into a sophisticated neural representation of our visual world. Specialized synapses, cells, and circuits in the retina have evolved to encode luminance, contrast, motion, and other complex visual features. Although a great deal has been learned about the cellular morphology and circuitry that underlies this image processing, many of the synapses in the retina remain incompletely understood. For example, excitatory synapses in the retina feature the full panoply of glutamate receptors, but in most cases specific roles for different receptor subtypes are unclear...
2011: Frontiers in Molecular Neuroscience
Craig M Smith, Philip J Ryan, Ihaia T Hosken, Sherie Ma, Andrew L Gundlach
The relaxin-3 gene was identified in 2001 by searching the human genome database for homologues of the relaxin hormone, and was subsequently discovered to encode a highly conserved neuropeptide in mammals and lower species. In the decade since its discovery there have been significant advances in our knowledge of the peptide, including the identification of its cognate receptor (a type 1 G-protein coupled receptor, GPCR135 or RXFP3), an understanding of its structure-activity and associated cellular signalling, and the elucidation of key neuroanatomical aspects of relaxin-3/RXFP3 networks in mammalian brain...
December 2011: Journal of Chemical Neuroanatomy
Alexander M Benison, Serhiy Chumachenko, Jacqueline A Harrison, Steven F Maier, Scott P Falci, Linda R Watkins, Daniel S Barth
Mechanical allodynia, the perception of innocuous tactile stimulation as painful, is a severe symptom of chronic pain often produced by damage to peripheral nerves. Allodynia affects millions of people and remains highly resistant to classic analgesics and therapies. Neural mechanisms for the development and maintenance of allodynia have been investigated in the spinal cord, brainstem, thalamus, and forebrain, but manipulations of these regions rarely produce lasting effects. We found that long-term alleviation of allodynic manifestations is produced by discreetly lesioning a newly discovered somatosensory representation in caudal granular insular cortex (CGIC) in the rat, either before or after a chronic constriction injury of the sciatic nerve...
April 27, 2011: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Kai Diederich, Wolf-Rüdiger Schäbitz, Jens Minnerup
Hematopoietic growth factors are known for their bolstering effects on the growth, survival, and differentiation of blood progenitor cells. Several of these cytokines also influence the proliferation of neural stem/progenitor cells, paralleling cellular mechanisms in analogy to their function in the hematopoietic system. Erythropoietin (EPO), granulocyte-colony stimulating factor (G-CSF), thrombopoietin (TPO), and their respective receptors are all expressed in the hippocampus of the mammalian brain. Recent studies have confirmed EPO and G-CSF as vital neurotrophic and neuroprotective factors, and ascertained their role in neuroprotection and neuroregeneration as pertaining to the most prominent neurodegenerative diseases...
May 2012: Hippocampus
Akihiko Ozawa, Iris Lindberg, Bryan Roth, Wesley K Kroeze
Peptide hormones and neuropeptides play important roles in endocrine and neural signaling, often using G protein-coupled receptor (GPCR)-mediated signaling pathways. However, the rate of novel peptide discovery has slowed dramatically in recent years. Genomic sequencing efforts have yielded a large number of cDNA sequences that potentially encode novel candidate peptide precursors, as well as hundreds of orphan GPCRs with no known cognate ligands. The complexity of peptide signaling is further highlighted by the requirement for specific posttranslational processing steps, and these must be accomplished in vitro prior to testing newly discovered peptide precursor candidates in receptor assays...
September 2010: AAPS Journal
Ming-Jie Yuan, Cong-Xin Huang, Yan-Hong Tang, Xi Wang, He Huang, Yong-Jun Chen, Tao Wang
Ghrelin is a newly discovered peptide as an endogenous ligand for the growth hormone secretagogue receptor, and has been demonstrated to exert beneficial effect in the cardiovascular system. In the present study, we investigated whether ghrelin administration could inhibit cardiac neural remodeling and sympathetic hyperinnervation after myocardial infarction. Sprague-Dawley rats underwent coronary ligation to induce myocardial infarction and receiving ghrelin chronically (100 microg/kg s.c., twice daily) or saline control for 4 weeks after onset of ischemia...
September 15, 2009: European Journal of Pharmacology
Gilbert M Rishton
Small molecule modulators of neural stem cell (NSC) differentiation might potentially be developed into orally administered neurogenic drugs to treat neurodegenerative diseases including Alzheimer's disease. New technologies developed for the study of NSC culture, proliferation and differentiation have enabled the establishment of screening platforms to identify small molecules with neurogenic activity. Recent patents claim novel small molecules identified from screening collections that stimulate or otherwise regulate stem cell differentiation and neurogenesis...
November 2008: Recent Patents on CNS Drug Discovery
Jiang-Hong Ye
Our knowledge of glycine receptor (GlyR) regulation of excitation has advanced significantly in recent years. GlyRs are widespread in the CNS, are heterogeneous, and undergo developmental changes. Activation of GlyRs of immature neurons induces outflow of Cl( - ), membrane depolarization, neuronal excitation, calcium influx, and transmitter release, in contrast to the inhibitory effects these receptors have in mature neurons. Thus, GlyRs are important for neuronal excitability in both the developing and the mature CNS...
2008: Results and Problems in Cell Differentiation
Kazuyoshi Tsutsui, George E Bentley, Takayoshi Ubuka, Etsuko Saigoh, Hong Yin, Tomohiro Osugi, Kazuhiko Inoue, Vishwajit S Chowdhury, Kazuyoshi Ukena, Nick Ciccone, Peter J Sharp, John C Wingfield
The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion. Gonadal sex steroids and inhibin inhibit gonadotropin secretion via feedback from the gonads, but a neuropeptide inhibitor of gonadotropin secretion was, until recently, unknown in vertebrates. In 2000, we identified a novel hypothalamic dodecapeptide that inhibits gonadotropin release in cultured quail pituitaries and termed it gonadotropin-inhibitory hormone (GnIH)...
August 2007: General and Comparative Endocrinology
Farshid Noorbakhsh, Nathalie Vergnolle, Justin C McArthur, Claudia Silva, Mohammed Vodjgani, Patricia Andrade-Gordon, Morley D Hollenberg, Christopher Power
Proteinase-activated receptors (PARs), a newly discovered subgroup of G-protein coupled receptors, are widely expressed by neural cells, but their roles in the nervous system remain uncertain. In this study, we report that PAR-2 was up-regulated on neurons in conjunction with neuroinflammation in brain tissue from patients with HIV-1-associated dementia. The inflammatory cytokines TNF-alpha and IL-1beta were also increased in HIV-1-associated dementia brains compared with patients without dementia (p < 0...
June 1, 2005: Journal of Immunology: Official Journal of the American Association of Immunologists
Sumana Shashidhar, Gustavo Lorente, Usha Nagavarapu, April Nelson, Jane Kuo, Jeramiah Cummins, Karoly Nikolich, Roman Urfer, Erik D Foehr
GPR56 (also known as TM7XN1) is a newly discovered orphan G-protein-coupled receptor (GPCR) of the secretin family that has a role in the development of neural progenitor cells and has been linked to developmental malformations of the human brain. GPR56 diverges from other secretin-like family members in that it has an extremely large N-terminal extracellular region (381 amino acids) and contains a novel feature among this new subclass, consisting of four cysteine residues that define a GPCR proteolytic site (GPS motif) located just before the first transmembrane spanning domain...
March 3, 2005: Oncogene
John W Wright, Joseph W Harding
The brain renin-angiotensin system (RAS) has long been known to regulate several classic physiologies including blood pressure, sodium and water balance, cyclicity of reproductive hormones and sexual behaviors, and pituitary gland hormones. These physiologies are thought to be under the control of the angiotensin II (AngII)/AT1 receptor subtype system. The AT2 receptor subtype is expressed during fetal development and is less abundant in the adult. This receptor appears to oppose growth responses facilitated by the AT1 receptor, as well as growth factor receptors...
March 2004: Progress in Neurobiology
Richard M Kostrzewa, Juan Segura-Aguilar
Cellular mechanisms involved in neurodegeneration and neuroprotection are continuing to be explored, and this paper focuses on some novel discoveries that give further insight into these processes. Oligodendrocytes and activated astroglia are likely generators of the pro-inflammatory cytokines, such as the tumor necrosis factor family and interleukin family, and these glial support cells express adhesion receptors (e.g., VCAM) and release intercellular adhesion molecules (ICAM) that have a major role in neuronal apoptosis...
2003: Neurotoxicity Research
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