Evidence map›Paper›PMID 30058008›Full record

ArticleJournal of molecular neuroscience : MN2019

PACAP/PAC1 Regulation of Inflammation via Catecholaminergic Neurons in a Model of Multiple Sclerosis.

Christina Van, Michael C Condro, Kenny Lov, Ruoyan Zhu, Patrick T Ricaflanca, Henly H Ko, Anna L Diep, Anh Q Hoang, Joseph Pisegna, Hermann Rohrer and 1 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular neuroscience : MN, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.3field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Stability Test of PACAP in Eye Drops.Journal of molecular neuroscience : MN · 2021
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Protective Effects of PACAP in Peripheral Organs.Frontiers in endocrinology · 2020
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Christina VanSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Michael C CondroSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Kenny LovSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Ruoyan ZhuSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Patrick T RicaflancaSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Henly H KoSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Anna L DiepSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Anh Q HoangSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Joseph PisegnaCenter for Ulcer Research and Education (CURE): Digestive Diseases Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
Hermann RohrerMax Planck Institute for Brain Research, Frankfurt, Germany.
James A WaschekSemel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, Intellectual and Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA, USA. jwaschek@mednet.ucla.edu.
University of California, Los Angeles · USMax Planck Institute for Brain Research · DE

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G · 1991 to 2018
$39.9M
Stem CellsP30HD004612 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARPENTER, ELLEN M. · 1985 to 2014
$19.5M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
UCLA Center for Translational Research in Neurodevelopment: UC-TRaNU54HD087101 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCCRACKEN, JAMES T. · 2016 to 2020
$6.5M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NCI NIH HHS P30 CA016042NIAID NIH HHS P30 AI028697NICHD NIH HHS P30 HD004612NICHD NIH HHS U54 HD087101NIDDK NIH HHS P30 DK041301NIH/NCATS UL1TR000124The National Multiple Sclerosis Society RG 1501-02646
6 · The paper itself

Abstract

The sympathetic nervous system (SNS) serves to maintain homeostasis of vital organ systems throughout the body, and its dysfunction plays a major role in human disease. The SNS also links the central nervous system to the immune system during different types of stress via innervation of the lymph nodes, spleen, thymus, and bone marrow. Previous studies have shown that pituitary adenylate cyclase-activating polypeptide (PACAP, gene name adcyap1) exhibits anti-inflammatory properties in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Because PACAP is known to regulate SNS function, we hypothesized that part of the immunoprotective action of PACAP is due to its neuromodulatory effects on sympathetic neurons. To examine this, we used an inducible, targeted approach to conditionally disrupt not only the PACAP-preferring PAC1 receptor gene (adcyap1r1) in dopamine β-hydroxylase-expressing cells, which includes postganglionic sympathetic neurons, but also catecholaminergic neurons in the brain and adrenomedullary chromaffin cells. In contrast to our previous EAE studies using PACAP global knockout mice which developed severe and prolonged EAE, we found that mice with conditional loss of PAC1 receptors in catecholaminergic cells developed a delayed time course of EAE with reduced helper T cell type 1 (Th1) and Th17 and enhanced Th2 cell polarization. At later time points, similar to mice with global PACAP loss, mice with conditional loss of PAC1 exhibited more severe clinical disease than controls. The latter was associated with a reduction in the abundance of thymic regulatory T cells (Tregs). These studies indicate that PAC1 receptor signaling acts in catecholaminergic cells in a time-dependent manner. At early stages of disease development, it enhances the ability of the SNS to polarize the Th response towards a more inflammatory state. Then, after disease is established, it enhances the ability of the SNS to dampen the inflammatory response via T

Indexed as

AnimalsChromaffin CellsDopaminergic NeuronsEncephalomyelitis, Autoimmune, ExperimentalMiceMice, Inbred C57BLPituitary Adenylate Cyclase-Activating PolypeptideReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type ISignal TransductionT-Lymphocytes, Helper-InducerT-Lymphocytes, RegulatoryAdcyap1r1 protein, mousePituitary Adenylate Cyclase-Activating PolypeptideReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type IExperimental autoimmune encephalomyelitisInflammationMultiple sclerosisPAC1PACAPRegulatory T cellsSympathetic nervous systemTamoxifenTh cells

Identifiers

PMID30058008
PMCPMC6353700
OpenAlexW2887532324

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.