Evidence map›Paper›PMID 34451870›Full record

ArticlePharmaceuticals (Basel, Switzerland)2021

Facilitation of TRKB Activation by the Angiotensin II Receptor Type-2 (AT2R) Agonist C21.

Liina Laukkanen, Cassiano R A F Diniz, Sebastien Foulquier, Jos Prickaerts, Eero Castrén, Plinio C Casarotto

Open access · goldAbstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. 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

6 authors at 3 institutions in 3 countries.

Liina LaukkanenNeuroscience Center, HiLife, University of Helsinki, 00014 Helsinki, Finland.
Cassiano R A F DinizDepartment of Pharmacology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Sebastien FoulquierDepartment of Pharmacology and Toxicology, CARIM-School for Cardiovascular Diseases, MHeNS-School for Mental Health and Neuroscience, Maastricht University, 6229 ER Maastricht, The Netherlands.ORCID 0000-0002-2523-0748
Jos PrickaertsDepartment of Psychiatry and Neuropsychology, MHeNS-School for Mental Health and Neuroscience, Maastricht University, 6229 ER Maastricht, The Netherlands.
Eero CastrénNeuroscience Center, HiLife, University of Helsinki, 00014 Helsinki, Finland.ORCID 0000-0002-1402-2791
Plinio C CasarottoNeuroscience Center, HiLife, University of Helsinki, 00014 Helsinki, Finland.ORCID 0000-0002-1090-4631
University of Helsinki · FIMaastricht University · NLUniversidade de São Paulo · BR

Funding

Academy of Finland 294710 and 307416EU Joint Programme - Neurodegenerative Disease Research 301225 and 643417European Research Council 322742
6 · The paper itself

Abstract

Blockers of angiotensin II type 1 receptor (AT1R) exert antidepressant-like effects by indirectly facilitating the activation of the angiotensin II type 2 receptor (AT2R), which leads to increased surface expression and transactivation of tropomyosin-related kinase B receptors (TRKB). Compound 21 (C21) is a non-peptide AT2R agonist that produces neuroprotective effects. However, the behavioral effects of C21 and its involvement with the brain-derived neurotrophic factor (BDNF)-TRKB system still need further investigation. The aim of the present study was to assess the effect of C21 on the activation of TRKB and its consequences on conditioned fear. The administration of C21 (0.1-10 μM/15 min) increased the surface levels of TRKB but was not sufficient to increase the levels of phosphorylated TRKB (pTRKB) in cultured cortical neurons from rat embryos. Consistent with increased TRKB surface expression, C21 (10 μM/15 min or 3 days) facilitated the effect of BDNF (0.1 ng/mL/15 min) on pTRKB in these cells. In contextual fear conditioning, the freezing time of C21-treated (administered intranasally) wild-type mice was decreased compared to the vehicle-treated group, but no effect of C21 was observed in BDNF.het animals. We observed no effect of C21 in the elevated plus-maze test for anxiety. Taken together, our results indicate that C21 facilitated BDNF effect by increasing the levels of TRKB on the cell surface and reduced the freezing time of mice in a BDNF-dependent manner, but not through a general anxiolytic-like effect.

Indexed as

angiotensin 2 type 2 receptor (AT2R)compound 21fear conditioningneurotrophin receptor type 2 (NTRK2)renin-angiotensin system (RAS)

Identifiers

PMID34451870
PMCPMC8400827
OpenAlexW3187466821

What Socratic 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 Socratic graph.