Evidence map›Paper›PMID 37958673›Full record

ArticleInternational journal of molecular sciences2023

Investigating the Effects of Exogenous and Endogenous 2-Arachidonoylglycerol on Retinal CB1 Cannabinoid Receptors and Reactive Microglia in Naive and Diseased Retina.

Sofia Papadogkonaki, Dimitris Spyridakos, Emmanouela Lapokonstantaki, Nikos Chaniotakis, Alexandros Makriyannis, Michael S Malamas, Kyriaki Thermos

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. 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

7 authors at 2 institutions in 2 countries.

Sofia PapadogkonakiDepartment of Pharmacology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
Dimitris SpyridakosDepartment of Pharmacology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.ORCID 0009-0002-5719-8911
Emmanouela LapokonstantakiDepartment of Chemistry, University of Crete, Heraklion, 71003 Crete, Greece.
Nikos ChaniotakisDepartment of Chemistry, University of Crete, Heraklion, 71003 Crete, Greece.ORCID 0000-0003-4281-1373
Alexandros MakriyannisCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Michael S MalamasCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Kyriaki ThermosDepartment of Pharmacology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
University of Crete · GRNortheastern University · US

Funding

Project 3 - In vivo pharmacology of cannabinoid receptor probesP01DA009158 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI Alexandros Makriyannis · 1994 to 2026
$26.0M
NIDA NIH HHS P01 DA009158
6 · The paper itself

Abstract

The endocannabinoid system (ECS) is a new target for the development of retinal disease therapeutics, whose pathophysiology involves neurodegeneration and neuroinflammation. The endocannabinoid 2-arachidonoylglycerol (2-AG) affects neurons and microglia by activating CB1/CB2 cannabinoid receptors (Rs). The aim of this study was to investigate the effects of 2-AG on the CB1R expression/downregulation and retinal neurons/reactive microglia, when administered repeatedly (4 d), in three different paradigms. These involved the 2-AG exogenous administration (a) intraperitoneally (i.p.) and (b) topically and (c) by enhancing the 2-AG endogenous levels via the inhibition (AM11920, i.p.) of its metabolic enzymes (MAGL/ABHD6). Sprague Dawley rats were treated as mentioned above in the presence or absence of CB1/CB2R antagonists and the excitatory amino acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Immunohistochemistry, Western blot and a 2-AG level analyses were performed. The 2-AG repeated treatment (i.p.) induced the CB1R downregulation, abolishing its neuroprotective actions. However, 2-AG attenuated the AMPA-induced activation of microglia via the CB2R, as concurred by the AM630 antagonist effect. Topically administered 2-AG was efficacious as a neuroprotectant/antiapoptotic and anti-inflammatory agent. AM11920 increased the 2-AG levels providing neuroprotection against excitotoxicity and reduced microglial activation without affecting the CB1R expression. Our findings show that 2-AG, in the three paradigms studied, displays differential pharmacological profiles in terms of the downregulation of the CB1R and neuroprotection. All treatments, however, attenuated the activation of microglia via the CB2R activation, supporting the anti-inflammatory role of 2-AG in the retina.

Indexed as

EndocannabinoidsMicrogliaalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidAnimalsArachidonic AcidsGlyceridesRatsRats, Sprague-DawleyReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Receptors, CannabinoidRetinaalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidArachidonic AcidsEndocannabinoidsGlyceridesglyceryl 2-arachidonateReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Receptors, Cannabinoid2-arachidonoylglycerolABHD6CB1 and CB2 cannabinoid receptorseye dropsMAGLmicroglianeuroinflammationneuroprotection

Identifiers

PMID37958673
PMCPMC10650178
OpenAlexW4388102519

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.