Pharmacological inhibition of NPY receptors illustrates dissociable features of experimental colitis in the mouse DSS model: Implications for preclinical evaluation of efficacy in an inflammatory bowel disease model

PloS One
Henry H RuizSusan D Croll

Abstract

Administration of dextran sodium sulfate (DSS) to rodents at varying concentrations and exposure times is commonly used to model human inflammatory bowel disease (IBD). Currently, the criteria used to assess IBD-like pathology seldom include surrogate measures of visceral pain. Thus, we sought to standardize the model and then identify surrogate measures to assess effects on visceral pain. We used various 4% DSS protocols and evaluated effects on weight loss, colon pathology, biochemistry, RNA signature, and open field behavior. We then tested the therapeutic potential of NPY Y1 and/or Y2 receptor inhibition for the treatment of IBD pathology using this expanded panel of outcome measures. DSS caused weight loss and colon shrinkage, increased colon NPY and inflammatory cytokine expression, altered behaviors in the open field and induced a distinct gene metasignature that significantly overlapped with that of human IBD patients. Inhibition of Y1 and/or Y2 receptors failed to improve gross colon pathology. Y1 antagonism significantly attenuated colon inflammatory cytokine expression without altering pain-associated behaviors while Y2 antagonism significantly inhibited pain-associated behaviors in spite of a limited effect on infla...Continue Reading

References

Sep 1, 1993·Digestive Diseases and Sciences·S N MurthyD J Sedergran
Jul 25, 2000·Postgraduate Medical Journal·T ShiraziC S Probert
Oct 2, 2002·Digestive Diseases and Sciences·Tessa ten HoveSander J H van Deventer
Oct 23, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hessameh HassaniPatrik Ernfors
Aug 27, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Raffaello FurlanAlberto Malliani
Sep 27, 2005·The American Journal of Gastroenterology·Raymond K CrossDavid G Binion
Dec 7, 2005·The Journal of Experimental Medicine·Julie WhewayFabienne Mackay
Dec 7, 2006·The American Journal of Pathology·John H ChidlowChristopher G Kevil
Jan 20, 2007·Autonomic Neuroscience : Basic & Clinical·Cormac T Taylor, Stephen J Keely
May 15, 2007·Lancet·Daniel C Baumgart, William J Sandborn
Mar 18, 2008·Journal of Neuroimmunology·Sammy BedouiStephan von Hörsten
Aug 21, 2008·Digestive Diseases and Sciences·Purnima SharmaKishore Kumar Deepak
Oct 7, 2008·PloS One·Bindu ChandrasekharanShanthi Srinivasan
Jan 9, 2009·Inflammatory Bowel Diseases·Klaus BielefeldtDavid G Binion
Jul 2, 2009·Clinical and Experimental Pharmacology & Physiology·Lysa BoisséAlan E Lomax
Sep 4, 2009·Journal of Clinical Gastroenterology·Ashwin N AnanthakrishnanDavid G Binion
Jun 10, 2010·International Journal of Colorectal Disease·Xue Hua PangHua Tian Gan
Oct 12, 2010·PloS One·Ilya KupershmidtMostafa Ronaghi
Jun 6, 2012·Journal of Biomedicine & Biotechnology·Martina Perše, Anton Cerar
Nov 2, 2012·The Journal of Pharmacology and Experimental Therapeutics·Shakir D AlSharariM Imad Damaj
Aug 31, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Vassilis ValatasGeorge Kolios
Oct 16, 2013·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Ji-Xiang ZhangWei-Guo Dong
Jan 15, 2014·Journal of Cellular and Molecular Medicine·Dileep G NairMichael G Blennerhassett
Jun 8, 2014·Inflammopharmacology·Nidhi GoyalPuneet Kumar
Sep 2, 2014·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Puneet Kaur RandhawaAmteshwar Singh Jaggi
Nov 28, 2014·Comprehensive Physiology·Kirsteen N Browning, R Alberto Travagli
May 23, 2015·Cellular and Molecular Gastroenterology and Hepatology·Patricia KieslerWarren Strober
Dec 5, 2015·Frontiers in Immunology·Martina Di GiovangiulioGianluca Matteoli
Oct 28, 2016·MMWR. Morbidity and Mortality Weekly Report·James M DahlhamerJanet B Croft

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
dissecting
protein assay
enzyme-linked immunosorbent assay

Software Mentioned

Illumina Casava
Graphpad Prism ( Prism
DESeq
Statistical Package for the Social Sciences ( SPSS
Image J
Bowtie
xPONENT
Motor Monitor

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.