Evidence map›Paper›PMID 40236188›Full record

ArticlebioRxiv : the preprint server for biology2025

Sex-specific proteomic analysis of epileptic brain tissues from Pten knockout mice and human refractory epilepsy.

Yibo Li, Zahra Sadri, Katherine J Blandin, David A Narvaiz, Uma K Aryal, Joaquin N Lugo, Nicholas P Poolos, Amy L Brewster

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Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Yibo Li
Zahra Sadri
Katherine J Blandin
David A Narvaiz
Nicholas P Poolos

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rationale: Epilepsy presents significant sex-based disparities in prevalence and manifestation. Epidemiological studies reveal that epilepsy is more prevalent in males, with lesional types being more common, whereas idiopathic generalized epilepsies are more frequently observed in females. These differences stress the importance of considering sex-specific factors in epilepsy diagnosis, treatment, and mechanistic research using preclinical models. To elucidate potential molecular differences that could explain these disparities and inform personalized treatment strategies, we conducted a proteomic analysis of epileptic brain tissues from both an experimental mouse model of genetic epilepsy and humans with drug-resistant epilepsy (DRE). Methods: We employed mass spectrometry-based proteomic analysis on brain tissues from DRE patients and the Results: PCA revealed distinct clustering of brain proteomes between epilepsy and control cases in both human and mice, with 390 proteins showing significant differences in human and 437 proteins in mouse samples. These proteins are primarily associated with ion channels, synaptic processes, and neuronal energy regulation. In the mouse model, males have more pronounced proteomic changes than females, with enrichment in metabolic pathways and VEGF signaling pathway, indicating a more severe vascular permeability impairment in males. In human DRE cases, 118 proteins were significantly changed by comparing epileptic females to males. Pathway analysis revealed changes in metabolic pathways and the HIF-1 signaling pathway, indicating that altered neuronal activity and inflammation may lead to increased oxygen consumption. Conclusion: These findings highlight significant differences between epilepsy and control brain samples in both humans and mice. Sex-specific analysis revealed distinct pathway enrichments between females and males, with males exhibiting a broader range of alterations, suggesting more extensive proteomic alterations. This study offers valuable insights into potential underlying mechanisms of epilepsy and underscores the importance of considering sex as a key factor in epilepsy research and therapeutic development.

Identifiers

PMID40236188
PMCPMC11996393

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