OSCR

<i>Blastocystis</i> sp. induces neurocognitive deficits in mice via p38 MAPK-mediated downregulation of NR4A1.

Overview

Authors: Xin Yang1, Huizhu Nan1, Yan Zhao1, Huan Li1, Xiangyun Zhang1, Mu He1, Lei Ma1
ORCID iDs: Lei Ma
  1. Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Collaborative Innovation Center for Eco-Environment, Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei Province, People's Republic of China
Institutions: Hebei Normal University (China)
Journal: Gut microbes, volume 18, issue 1, article 2659393
Dates: received 23 September 2025; accepted 9 April 2026; published online 14 April 2026; in print December 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1080/19490976.2026.2659393 · PMID 41981757 · PMCID PMC13081747 · OpenAlex W7154471118
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: histology / microscopy (modality), mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics, Graphs
Keywords: Blastocystis sp, neurocognitive deficits, p38 MAPK, NR4A1
MeSH: Blastocystis*, Blastocystis Infections*, Nuclear Receptor Subfamily 4, Group A, Member 1*, p38 Mitogen-Activated Protein Kinases*, Animals, Brain, Down-Regulation, Interleukin-17, Male, Mice, Mice, Inbred C57BL, Microglia, Signal Transduction (* major topic)
Topic: Parasitic Infections and Diagnostics (Parasitology, Immunology and Microbiology), according to OpenAlex
Funding: Hebei Normal University; National Natural Science Foundation of China (H202105002)
Citations: not cited yet (Europe PMC); 72 references in the paper

Abstract

Blastocystis sp. is a zoonotic protozoan with a broad host range, and its pathogenicity in humans has remained controversial. In this study, we observed neurocognitive impairments in mice following Blastocystis sp. infection, prompting us to investigate the mechanisms underlying these changes. Transcriptomic analysis of brain tissue revealed significant changes in the expression of several Neurocognitive Deficits -associated genes, most notably a marked downregulation of the nuclear receptor NR4A1. These findings were validated and confirmed using Western blot, immunofluorescence, and immunohistochemical analyses. While in vitro infection of BV2 microglial cells with Blastocystis sp. revealed activation of the IL-17-p38 MAPK-NR4A1 signaling axis, in vivo administration of a p38 inhibitor in infected mice ameliorated motor and cognitive deficits, demonstrating that this signaling cascade mediates neuropathology in mouse brain following the parasite infection. This finding indicates that Blastocystis sp. infection induces IL-17 overexpression in both the gut and brain, resulting in the activation of the p38 MAPK pathway. This subsequently leads to significant NR4A1 downregulation and, ultimately, results in Neurocognitive Impairment behavioral phenotypes in mice. This study reveals a novel mechanism whereby Blastocystis sp. infection induces cognitive and motor deficits through activation of the p38 MAPK-NR4A1 pathway in brain tissue, offering a potential therapeutic target for future interventions.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

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Data

Datasets cited

Data availability statement

The raw data supporting the conclusions of this study have been deposited in the Mendeley Data repository. They are publicly available and can be accessed at the following link: https://data.mendeley.com/preview/m44v6brrph?a=01d4ca1b-36b3-49ea-aa63-3fbeb36885a9.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 4 keywords, 13 MeSH terms, 2 funders, 71 references.

Cite

This paper

Yang, X., Nan, H., Zhao, Y., Li, H., Zhang, X., He, M., & Ma, L. (2026). <i>Blastocystis</i> sp. induces neurocognitive deficits in mice via p38 MAPK-mediated downregulation of NR4A1. Gut microbes, 18(1), 2659393. https://doi.org/10.1080/19490976.2026.2659393

BibTeX

@article{yang2026lt,
author = {Yang, Xin and Nan, Huizhu and Zhao, Yan and Li, Huan and Zhang, Xiangyun and He, Mu and Ma, Lei},
title = {{\<i\>Blastocystis\</i\> sp. induces neurocognitive deficits in mice via p38 MAPK-mediated downregulation of NR4A1}},
journal = {Gut microbes},
year = {2026},
month = apr,
volume = {18},
number = {1},
pages = {2659393},
publisher = {Taylor \& Francis},
issn = {1949-0976},
doi = {10.1080/19490976.2026.2659393},
url = {https://doi.org/10.1080/19490976.2026.2659393},
pmid = {41981757},
pmcid = {PMC13081747}
}

RIS

TY - JOUR
AU - Yang, Xin
AU - Nan, Huizhu
AU - Zhao, Yan
AU - Li, Huan
AU - Zhang, Xiangyun
AU - He, Mu
AU - Ma, Lei
TI - <i>Blastocystis</i> sp. induces neurocognitive deficits in mice via p38 MAPK-mediated downregulation of NR4A1
T2 - Gut microbes
J2 - Gut Microbes
PY - 2026
DA - 2026/04/14
VL - 18
IS - 1
SP - 2659393
SN - 1949-0976
PB - Taylor & Francis
DO - 10.1080/19490976.2026.2659393
UR - https://doi.org/10.1080/19490976.2026.2659393
LA - en
ER -

CSL-JSON

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