Evidence map›Paper›PMID 39475992›Full record

ArticlePloS one2024

SARS-CoV-2 propagation to the TPH2-positive neurons in the ventral tegmental area induces cell death via GSK3β-dependent accumulation of phosphorylated tau.

Motoki Imai, Fumitaka Kawakami, Takayuki Uematsu, Toshihide Matsumoto, Rei Kawashima, Yoshifumi Kurosaki, Shun Tamaki, Shotaro Maehana, Takafumi Ichikawa, Hideaki Hanaki and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2024. 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
–field-weighted citation impact
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.

  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

12 authors.

Motoki ImaiDepartment of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Fumitaka KawakamiRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Takayuki UematsuBiomedical Laboratory, Division of Biomedical Research, Kitasato University Medical Center, Kitamoto, Saitama, Japan.
Toshihide MatsumotoRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Rei KawashimaRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Yoshifumi KurosakiRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Shun TamakiRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.ORCID 0009-0009-7722-5623
Shotaro MaehanaRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Takafumi IchikawaRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Hideaki HanakiInfection Control Research Center, Ōmura Satoshi Memorial Institute, Kitasato University, Minato-Ku, Tokyo, Japan.
Hidero KitazatoRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Makoto KuboRegenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.ORCID 0000-0001-8264-1343

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

COVID-19, an infectious disease caused by SARS-CoV-2, was declared a pandemic by the WHO in 2020. Psychiatric symptoms including sleep disturbance, memory impairment, and depression are associated with SARS-CoV-2 infection. These symptoms are causes long-term mental and physical distress in recovering patients; however, the underlying mechanism is unclear. In this study, we determined the effects of SARS-CoV-2 infection on brain tissue using k18hACE2 mice. Using brain tissue from 18hACE2 mice infected with SARS-CoV-2 through intranasal administration, SARS-CoV-2 spike protein and RNA were analyzed by immunohistochemical staining and in-situ hybridization. Immunohistochemical analysis revealed that Tryptophan hydroxylase 2 (TPH2)-positive cells and SARS-CoV-2 spike protein were co-localized in the ventral tegmental area of SARS-CoV-2-infected mice. We observed decreased TPH2 expression and increased accumulation of phosphorylated tau protein and Phospho-Histone H2A.X (γH2AX) expression in the ventral tegmental region. In addition, activation of glycogen synthase kinase 3β (GSK3β) was induced by SARS-CoV-2 infection. Overall, our results suggest that SARS-CoV-2 infection of TPH2-positive cells in the ventral tegmental area induces neuronal cell death through increased accumulation of phosphorylated tau. Attenuation of the GSK3β pathway and decreased serotonin synthesis through suppression of TPH2 expression may contribute to the development of neurological symptoms.

Indexed as

COVID-19Glycogen Synthase Kinase 3 betaNeuronsSARS-CoV-2tau ProteinsTryptophan HydroxylaseVentral Tegmental AreaAnimalsCell DeathHumansMaleMiceMice, TransgenicPhosphorylationSpike Glycoprotein, CoronavirusGlycogen Synthase Kinase 3 betaGsk3b protein, mouseSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2tau ProteinsTph2 protein, mouseTryptophan Hydroxylase

Identifiers

PMID39475992
PMCPMC11524480

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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.