Amino acid- and lipid-related metabolic remodeling in PTZ-kindled mice reveals candidate plasma signatures of chronic epilepsy.

Overview

1. Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China

Abstract

Background: Metabolic dysfunction is increasingly implicated in epilepsy, but the systemic metabolic alterations associated with chronic seizures remain incompletely characterized. This study aimed to define peripheral metabolic signatures of chronic epilepsy in a pentylenetetrazol (PTZ)-kindled mouse model and to examine whether the altered pathways were supported by human epilepsy transcriptomic data.

Methods: Male C57BL/6 mice were subjected to repeated PTZ injections to establish chronic epilepsy, while control mice received saline. Plasma samples were analyzed using ultra-high-performance liquid chromatography-mass spectrometry-based untargeted metabolomics. Differential metabolites were identified through multivariate and univariate analyses, followed by KEGG pathway enrichment. Least absolute shrinkage and selection operator (LASSO) regression was used as an exploratory feature-selection method. To provide complementary human hippocampal transcriptomic context, the hippocampal subset of GSE256068 was reanalyzed using differential expression analysis, and KEGG pathway enrichment analysis.

Results: PTZ-kindled mice displayed a distinct plasma metabolic profile compared with controls. A total of 349 differential metabolites were identified, mainly enriched in amino acid metabolism, tryptophan metabolism, and central carbon metabolism. LASSO regression identified six candidate metabolic features, all of which are reported in the supplementary material. Among them, indolelactic acid (ILA) and DG (20:3n6/0:0/20:3n6) were prioritized for biological interpretation because of their relevance to tryptophan-related and lipid-related metabolism. Reanalysis of the human hippocampal transcriptomic dataset revealed pathway-level alterations related to GABAergic synaptic signaling, glycosphingolipid biosynthesis, inflammatory regulation of TRP channels, and inflammatory response, providing complementary human hippocampal context for the neurotransmitter-, lipid-, and inflammatory--related metabolic alterations observed in PTZ-kindled mice.

Conclusion: PTZ-induced kindling was associated with marked plasma metabolic alterations involving amino acid-, tryptophan-, and lipid-related pathways. ILA and DG (20:3n6/0:0/20:3n6) emerged as candidate plasma metabolic features associated with the PTZ-kindled seizure phenotype. Complementary analysis of human temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) hippocampal transcriptomic data identified related alterations in neurotransmission-, lipid-, and inflammatory-associated pathways. This pathway-level convergence supports the broader relevance of metabolic dysregulation to epilepsy, while the mechanistic roles and biomarker potential of individual metabolites require independent validation.

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

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• geo:GSE256068, at NCBI GEO; found in “Data availability statement”

Data availability statement

Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE256068.

Reproduced under the paper's license (CC BY), 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, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 5 authors, 7 keywords, 46 references.

Cite

This paper

Ren, J., Wang, F., Li, Z., Liang, Z., & Liu, S. (2026). Amino acid- and lipid-related metabolic remodeling in PTZ-kindled mice reveals candidate plasma signatures of chronic epilepsy. Frontiers in neuroscience, 20, 1889410. https://doi.org/10.3389/fnins.2026.1889410

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1080/19490976.2026.2659400 [code]

Microbiome signatures correlate with diet-mediated ADHD symptom reduction.

Journal: Gut microbes

In common: clinical / translational, genetics / omics, 3 references

[2] doi:10.1002/ana.78283

Gut-Brain Axis Modulation by Short-Chain Fatty Acids Exerts Disease-Modifying Effects in a Murine Model of Drug-Resistant Epilepsy.

Journal: Annals of neurology

In common: epilepsy, clinical / translational, mouse, 2 references

[3] doi:10.1038/s41467-026-73796-5 [code]

Cross-species transcriptomic analysis of rodent model fidelity to human mesial temporal lobe epilepsy.

Journal: Nature communications

In common: epilepsy, genetics / omics, mouse, 2 references

[4] doi:10.1186/s12974-026-03951-8

Forkhead box versus NF-κB hippocampal snRNA-seq profiles distinguish anti-Drebrin- and anti-GAD65-positive encephalitis.

Journal: Journal of neuroinflammation

In common: epilepsy, genetics / omics, mouse, 1 reference

[5] doi:10.1186/s12915-026-02635-2 [code]

Microbial enterotype is linked to episodic and working memories via brain function in the parietal and occipital cortices.

Journal: BMC biology

In common: 2 references

[6] doi:10.3390/ijms27104466 [code]

Uncovering the Key Circuit FOSL2/FOS/EGR3/EGR1, Contributing to the Hyperexcitability of Excitatory Neurons in the Epileptic Temporal Cortex and Hippocampus.

Journal: International journal of molecular sciences

In common: epilepsy, genetics / omics, 1 reference

[7] doi:10.1038/s41593-026-02384-z [code]

cGAS-mediated type I IFN signaling contributes to disease progression in drug-refractory epilepsy.

Journal: Nature neuroscience

In common: epilepsy, mouse, 1 reference

[8] doi:10.1007/s12035-026-06155-6

Sigma-1 Expression in Chronic Mouse Models of Temporal Lobe Epilepsy.

Journal: Molecular neurobiology

In common: epilepsy, mouse, 1 reference

[9] doi:10.1016/j.isci.2026.116622 [code]

Multi-omics profiling reveals gut microbiome signatures associated with cognitive decline in Alzheimer's disease.

Journal: iScience

In common: clinical / translational, genetics / omics, 1 reference

[10] doi:10.3389/fcell.2026.1793636

Pyroptosis in epilepsy: from pathophysiological mechanisms to therapeutic strategies.

Journal: Frontiers in cell and developmental biology

In common: epilepsy, 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.