Evidence map›Paper›PMID 34440670›Full record

ReviewCells2021

Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia-Relevance for Mental Diseases.

Dasiel O Borroto-Escuela, Patrizia Ambrogini, Manuel Narvaez, Valentina Di Liberto, Sarah Beggiato, Luca Ferraro, Ramon Fores-Pons, Jose E Alvarez-Contino, Alexander Lopez-Salas, Giuseppa Mudò and 2 more

Open access · goldAbstract readReview
In one paragraph

Review in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

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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

12 authors at 6 institutions in 3 countries.

Dasiel O Borroto-EscuelaDepartment of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.ORCID 0000-0002-5736-373X
Patrizia AmbroginiDepartment of Biomolecular Science Section of Morphology, Physiology and Environmental Biology, Campus Scientifico Enrico Mattei, via Ca' le Suore 2, 61029 Urbino, Italy.ORCID 0000-0002-3195-0725
Manuel NarvaezFacultad de Medicina, Instituto de Investigacion de Málaga, Universidad de Malaga, Campus de Teatinos s/n, 29071 Málaga, Spain.ORCID 0000-0003-0922-4900
Valentina Di LibertoDepartment of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, 90134 Palermo, Italy.
Sarah BeggiatoDepartment of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, 66100 Chieti, Italy.
Luca FerraroDepartment of Life Sciences and Biotechnology and LTTA Center, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0003-2390-6414
Ramon Fores-PonsDepartment of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Jose E Alvarez-ContinoDepartment of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Alexander Lopez-SalasDepartment of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Giuseppa MudòDepartment of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, 90134 Palermo, Italy.ORCID 0000-0002-3275-9981
Zaida Díaz-CabialeFacultad de Medicina, Instituto de Investigacion de Málaga, Universidad de Malaga, Campus de Teatinos s/n, 29071 Málaga, Spain.
Kjell FuxeDepartment of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.ORCID 0000-0001-8491-4288
Karolinska Institutet · SEUniversidad de Málaga · ESUniversity of Palermo · ITFondazione Eni Enrico Mattei · ITUniversity of Chieti-Pescara · ITUniversity of Ferrara · IT

Funding

EMERGIA EMERGIA20-39318Hjärnfonden F02018-0286Hjärnfonden F02019-0296Karolinska Institutet Forskningsstiftelser Borroto-Escuela 2020Stiftelsen Olle Engkvist Byggmästare Fuxe 2019Vetenskapsrådet 62X-00715-50-3
6 · The paper itself

Abstract

The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor-receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biological principle of forming 5-HT and other heteroreceptor complexes in the brain also help understand the mechanism of action for especially the 5-HT hallucinogens, including putative positive effects of e.g., psilocybin and the indicated prosocial and anti-stress actions of MDMA (ecstasy). The GalR1-GalR2 heterodimer and the putative GalR1-GalR2-5-HT1 heteroreceptor complexes are targets for Galanin N-terminal fragment Gal (1-15), a major modulator of emotional networks in models of mental disease. GPCR-receptor tyrosine kinase (RTK) heteroreceptor complexes can operate through transactivation of FGFR1 via allosteric mechanisms and indirect interactions over GPCR intracellular pathways involving protein kinase Src which produces tyrosine phosphorylation of the RTK. The exciting discovery was made that several antidepressant drugs such as TCAs and SSRIs as well as the fast-acting antidepressant drug ketamine can directly bind to the TrkB receptor and provide a novel mechanism for their antidepressant actions. Understanding the role of astrocytes and their allosteric receptor-receptor interactions in modulating forebrain glutamate synapses with impact on dorsal raphe-forebrain serotonin neurons is also of high relevance for research on major depressive disorder.

Indexed as

Receptor Cross-TalkAnimalsAntidepressive AgentsAntipsychotic AgentsAstrocytesBrainDopaminergic NeuronsHumansMental DisordersReceptor, Fibroblast Growth Factor, Type 1Receptor, Galanin, Type 1Receptor, Galanin, Type 2Receptors, Dopamine D2Receptor, Serotonin, 5-HT2AReceptors, Serotonin, 5-HT1Serotonergic NeuronsAntidepressive AgentsAntipsychotic AgentsReceptor, Fibroblast Growth Factor, Type 1Receptor, Galanin, Type 1Receptor, Galanin, Type 2Receptors, Dopamine D2Receptor, Serotonin, 5-HT2AReceptors, Serotonin, 5-HT1astrogliadepressionG protein-coupled receptorsheteroreceptor complexesrapid antidepressant drugsreceptor tyrosine kinaseserotonin receptors

Identifiers

PMID34440670
PMCPMC8392445
OpenAlexW3184995356

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.