Evidence map›Paper›PMID 26581500›Full record

ArticleNeuropharmacology2016

Functional modulation of G-protein coupled receptors during Parkinson disease-like neurodegeneration.

Bruce G Jenkins, Aijun Zhu, Pekka Poutiainen, Ji-Kyung Choi, Kun-Eek Kil, Zhaoda Zhang, Darshini Kuruppu, Nurgul Aytan, Alpaslan Dedeoglu, Anna-Liisa Brownell

Abstract read
In one paragraph

Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Bruce G JenkinsAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA.
Aijun ZhuAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA.
Pekka PoutiainenAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA.
Ji-Kyung ChoiAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA.
Kun-Eek KilAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA.
Zhaoda ZhangAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA.
Darshini KuruppuSurgical Oncology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Nurgul AytanDepartment of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA.
Alpaslan DedeogluDepartment of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
Anna-Liisa BrownellAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA. Electronic address: abrownell@partners.org.
Massachusetts General Hospital · USAthinoula A. Martinos Center for Biomedical Imaging · USVA Boston Healthcare System · US

Funding

Positive Allosteric Modulators as PET Imaging Ligans for mGluR4R01NS100164 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI BROWNELL, ANNA-LIISA, ZHANG, ZHAODA · 2016 to 2020
$3.7M
Positive allosteric modulators as PET imaging ligands for mGluR4R01EB012864 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI BROWNELL, ANNA-LIISA · 2011 to 2014
$2.2M
Targeting Glial mGluR5 in SchizophreniaR01MH091684 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI BROWNELL, ANNA-LIISA, CICCHETTI, FRANCESCA · 2010 to 2013
$1.2M
Activatable MR Imaging ProbesR01CA161221 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CARAVAN, PETER D · 2011 to 2014
$1.1M
500 MHz NMR Spectrometer for Molecular Imaging ApplicationsS10RR023385 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2007 to 2007
$500k
F-18 SynthesizerS10RR023452 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI BROWNELL, ANNA-LIISA · 2007 to 2007
$500k
Carbon-11 Radiopharmaceutical Production SystemS10RR026666 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI BROWNELL, ANNA-LIISA · 2010 to 2010
$462k
NCI NIH HHS R01 CA161221NCRR NIH HHS S10 RR023385NCRR NIH HHS S10 RR023452NCRR NIH HHS S10 RR026666NIBIB NIH HHS R01 EB012864NIMH NIH HHS R01 MH091684NINDS NIH HHS R01 NS100164
6 · The paper itself

Abstract

G-protein coupled dopamine and metabotropic glutamate receptors (mGlu) can modulate neurotransmission during Parkinson's disease (PD)-like neurodegeneration. PET imaging studies in a unilateral dopamine denervation model (6-OHDA) showed a significant inverse correlation of presynaptic mGlu4 and postsynaptic mGlu5 expression in the striatum and rapidly declining mGlu4 and enhanced mGlu5 expression in the hippocampus during progressive degeneration over time. Immunohistochemical studies verified the decreased mGlu4 expression in the hippocampus on the lesion side but did not show difference in mGlu5 expression between lesion and control side. Pharmacological MRI studies showed enhanced hemodynamic response in several brain areas on the lesion side compared to the control side after challenge with mGlu4 positive allosteric modulator or mGlu5 negative allosteric modulator. However, mGlu4 response was biphasic having short enhancement followed by negative response on both sides of brain. Studies in mGlu4 expressing cells demonstrated that glutamate induces cooperative increase in binding of mGlu4 ligands - especially at high glutamate levels consistent with in vivo concentration. This suggests that mGlu allosteric modulators as drug candidates will be highly sensitive to changes in glutamate concentration and hence metabolic state. These experiments demonstrate the importance of the longitudinal imaging studies to investigate temporal changes in receptor functions to obtain individual response for experimental drugs.

Indexed as

AnimalsCHO CellsCricetinaeCricetulusDose-Response Relationship, DrugGlutamic AcidMaleNeurodegenerative DiseasesParkinsonian DisordersProtein BindingRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, Metabotropic GlutamateGlutamic Acidmetabotropic glutamate receptor 4Receptors, G-Protein-CoupledReceptors, Metabotropic GlutamateMetabotropic glutamate receptormGlu(4)mGlu(5)Parkinson's diseasePharmacological magnetic resonance imagingPositron emission tomography

Identifiers

PMID26581500
PMCPMC4896842
OpenAlexW2181119163

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.