Evidence map›Paper›PMID 41824475›Full record

ArticlePLoS neglected tropical diseases2026

Acod1/itaconate axis controls anxiety-like behaviors induced by chronic infection of Toxoplasma gondii in mice.

Ziyi Yan, Yumeng Zhou, Yingting Huang, Huiling Lv, Siyu Li, Yifan Zhang, Yan He, Xinde Jiang, Heng Deng, Yujuan Shen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS neglected tropical diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Ziyi YanJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yumeng ZhouJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yingting HuangJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Huiling LvJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Siyu LiJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yifan ZhangJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yan HeJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Xinde JiangJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Heng DengJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Yujuan ShenNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, Shanghai, China.
Yumei ZhangDepartment of Pathogenic Biology, Binzhou Medical University, Yantai, Shandong, China.
Wei PanJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.ORCID https://orcid.org/0000-0003-2641-1759
Fenfen SunJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic infection of Toxoplasma gondii (T. gondii) induces the anxiety-like behavior in hosts, which is closely linked to neuroinflammatory processes. Cis-aconite decarboxylase 1 (Acod1) is an enzyme that is responsible for itaconate production in Krebs Cycle. Emerging evidence highlights the Acod1/itaconate axis as a key regulatory node in macrophage immune-metabolic reprogramming. However, its role in infection-induced neurobehavioral alterations remains unclear. Here, we investigated the role of Acod1/itaconate axis in the anxiety induced by T. gondii chronic infection in mice.

methodsTo assess anxiety-like behaviors, we performed open field test and elevated plus maze test. Transcriptomic alterations and neuroinflammatory responses in the mouse amygdala were profiled via RNA sequencing, immunofluorescence staining, quantitative PCR (qPCR), and western blot. The functional role of the Acod1/itaconate axis was further investigated using Acod1-/- mice. Additionally, the therapeutic potential of dimethyl itaconate (DI), a cell-permeable itaconate derivative, was evaluated in chronically T. gondii-infected mice. The levels of indoleamine 2,3-dioxygenase (IDO), and serotonin (5-hydroxytryptamine, 5-HT) in serum were measured by enzyme-linked immunosorbent assay. Finally, DI's anti-inflammatory mechanism was identified in the microglial cell line BV-2 cells.

resultsChronic T. gondii infection induced anxiety-like behaviors in mice and triggered the activation of Acod1/itaconate axis in the amygdala. Transcriptomic and histological analyses revealed upregulation of neuroinflammation-related genes, along with microglia activation. Genetic knockout of Acod1 induced the anxiety-like phenotypes, which were rescued by DI administration. Notably, DI treatment conferred both prophylactic and therapeutic benefits, effectively mitigating anxiety induced by infection. Mechanistically, DI suppressed T. gondii-induced M1 polarization in microglia to mitigate neuroinflammation via activating Nrf2 signaling. These events further reduced indoleamine IDO expression, leading to increased 5-HT levels and subsequent amelioration of anxiety-like behavior.

conclusionsOur findings demonstrate that the Acod1/itaconate axis plays an important role in regulating anxiety-like behavior by modulating neuroinflammation during chronic T. gondii infection. These results reveal a promising immune-metabolic drug target for treating T. gondii-associated neuropsychiatric conditions.

Indexed as

AnxietyCarboxy-LyasesSuccinatesToxoplasmosis, AnimalAmygdalaAnimalsBehavior, AnimalChronic DiseaseDisease Models, AnimalFemaleHydro-LyasesIndoleamine-Pyrrole 2,3,-DioxygenaseMaleMiceMice, Inbred C57BLMice, KnockoutAcod1 protein, mouseCarboxy-LyasesHydro-LyasesIndoleamine-Pyrrole 2,3,-Dioxygenaseitaconic acidSuccinates

Identifiers

PMID41824475
PMCPMC12987495

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.