Evidence map›Paper›PMID 33383868›Full record

ArticleInternational journal of molecular sciences2020

Serotonin/5-HT1A Signaling in the Neurovascular Unit Regulates Endothelial CLDN5 Expression.

Kotaro Sugimoto, Naoki Ichikawa-Tomikawa, Keisuke Nishiura, Yasuto Kunii, Yasuteru Sano, Fumitaka Shimizu, Akiyoshi Kakita, Takashi Kanda, Tetsuya Imura, Hideki Chiba

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-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

7 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Serotonergic regulation of cortical neurovascular coupling and hemodynamics upon awakening from sleep in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
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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

10 authors at 3 institutions in 1 country.

Kotaro SugimotoDepartment of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.ORCID 0000-0002-5299-7610
Naoki Ichikawa-TomikawaDepartment of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Keisuke NishiuraDepartment of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Yasuto KuniiDepartment of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Yasuteru SanoDepartment of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
Fumitaka ShimizuDepartment of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
Akiyoshi KakitaDepartment of Pathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.ORCID 0000-0003-4244-0277
Takashi KandaDepartment of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
Tetsuya ImuraDepartment of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Hideki ChibaDepartment of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.ORCID 0000-0003-1777-8460
Fukushima Medical University · JPYamaguchi University · JPNiigata University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We previously reported that site-selective claudin-5 (CLDN5) breakdown and protein kinase A (PKA) activation are observed in brain microvessels of schizophrenia, but the underlying molecular basis remains unknown. The 5-HT1 receptors decline the intracellular cAMP levels and inactivate the major downstream PKA, and the 5-HT1A receptor is a promising target for schizophrenia. Therefore, we elucidated the involvement of serotonin/5-HT1A signaling in the endothelial CLDN5 expression. We demonstrate, by immunohistochemistry using post-mortem human brain tissue, that the 5-HT1A receptor is expressed in brain microvascular endothelial cells (BMVECs) and mural cells of the normal prefrontal cortex (PFC) gray matter. We also show that PKA is aberrantly activated not only in BMVECs but also in mural cells of the schizophrenic PFC. We subsequently revealed that the endothelial cell-pericyte tube-like structure was formed in a novel two-dimensional co-culture of human primary BMVECs and a human brain-derived pericyte cell line, in both of which the 5-HT1A receptor was expressed. Furthermore, we disclose that the serotonin/5-HT1A signaling enhances endothelial CLDN5 expression in BMVECs under two-dimensional co-culture conditions. Our findings provide novel insights into the physiological and pathological significance of serotonin/5-HT1A signaling in the region-specific regulation of the blood-brain barrier.

Indexed as

Gene Expression RegulationNeurovascular CouplingSignal TransductionBiomarkersBrainCell CommunicationClaudin-5Cyclic AMP-Dependent Protein KinasesEndothelial CellsFluorescent Antibody TechniqueHumansPericytesReceptor, Serotonin, 5-HT1ASerotoninBiomarkersClaudin-5CLDN5 protein, humanCyclic AMP-Dependent Protein KinasesReceptor, Serotonin, 5-HT1ASerotonin5-HT1 receptorblood-brain barrierclaudinco-cultureendothelial cellpericytePKApsychiatric disorderschizophreniatight junction

Identifiers

PMID33383868
PMCPMC7795278
OpenAlexW3114880335

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Registered trials

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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.