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Peer-reviewedCC BYFrontiers in neurology

Cross-dataset transcriptomics–proteomics analysis identifies Tlr2, Anxa5, and Grin2a as candidate mouse-brain signatures associated with chronic cerebral hypoperfusion

  • Xiang Fan1
  • Meng-Yu Zhong2
  • Huan Liu2
  • Hao Tao1
  • Yi Li1
  • Xun Wu2
  • Ying-jie Li2
  • Bing-Hu Li1
  • Neng-Wei Yu1
  1. 1School of Medicine, University of Electronic Science and Technology of China , ,
  2. 2Department of Neurology, Sichuan Provincial People's Hospital , ,
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Abstract

Background: Chronic cerebral hypoperfusion (CCH) is a neurological disorder characterized by persistent insufficiency of cerebral blood flow, yet specific biomarkers and mechanistic insights are lacking.

Methods: This study integrated transcriptomic and proteomic multi-omics analyses, along with behavioral assessments and immunofluorescence validation in a bilateral common carotid artery stenosis (BCAS) mouse model, to identify and validate candidate multi-omics biomarkers of CCH and explore their potential druggability. Leveraging public transcriptomic datasets and in-house proteomic data, differential expression analysis, protein-protein interaction network construction, and five topological algorithms identified Tlr2 , Anxa5 , and Grin2a as candidate biomarkers.

Results: BCAS mice exhibited spatial memory impairments in behavioral tests. Immunofluorescence revealed upregulated TLR2 and ANXA5 , downregulated GRIN2A, and increased TLR2-IBA1 co-localization indicating microglial activation. Tlr2 and Anxa5 positively correlated with infiltrating immune cells, whereas Grin2a showed a negative correlation. A putative ceRNA network and in silico molecular docking suggested strong binding of pirinixic acid to both TLR2 and ANXA5.

Discussion: Tlr2 , Anxa5 , and Grin2a can serve as candidate multi-omics signature molecules of CCH in the mouse brain, with consistent alterations at the transcriptomic, proteomic, and tissue levels.

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Cite

BibTeXRIS
BibTeX
@article{fan2026crossdataset,
  title = {{Cross-dataset transcriptomics–proteomics analysis identifies Tlr2, Anxa5, and Grin2a as candidate mouse-brain signatures associated with chronic cerebral hypoperfusion}},
  author = {Xiang Fan and Meng-Yu Zhong and Huan Liu and Hao Tao and Yi Li and Xun Wu and Ying-jie Li and Bing-Hu Li and Neng-Wei Yu},
  journal = {Frontiers in neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1911864},
  url = {https://europepmc.org/article/PMC/PMC13668749},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cross-dataset transcriptomics–proteomics analysis identifies Tlr2, Anxa5, and Grin2a as candidate mouse-brain signatures associated with chronic cerebral hypoperfusion
AU  - Xiang Fan
AU  - Meng-Yu Zhong
AU  - Huan Liu
AU  - Hao Tao
AU  - Yi Li
AU  - Xun Wu
AU  - Ying-jie Li
AU  - Bing-Hu Li
AU  - Neng-Wei Yu
PY  - 2026
DA  - 2026/10/01
JO  - Frontiers in neurology
DO  - 10.3389/fneur.2026.1911864
UR  - https://europepmc.org/article/PMC/PMC13668749
AB  - Background: Chronic cerebral hypoperfusion (CCH) is a neurological disorder characterized by persistent insufficiency of cerebral blood flow, yet specific biomarkers and mechanistic insights are lacking.  Methods: This study integrated transcriptomic and proteomic multi-omics analyses, along with behavioral assessments and immunofluorescence validation in a bilateral common carotid artery stenosis (BCAS) mouse model, to identify and validate candidate multi-omics biomarkers of CCH and explore their potential druggability. Leveraging public transcriptomic datasets and in-house proteomic data, differential expression analysis, protein-protein interaction network construction, and five topological algorithms identified Tlr2 , Anxa5 , and Grin2a as candidate biomarkers.  Results: BCAS mice exhibited spatial memory impairments in behavioral tests. Immunofluorescence revealed upregulated TLR2 and ANXA5 , downregulated GRIN2A, and increased TLR2-IBA1 co-localization indicating microglial activation. Tlr2 and Anxa5 positively correlated with infiltrating immune cells, whereas Grin2a showed a negative correlation. A putative ceRNA network and in silico molecular docking suggested strong binding of pirinixic acid to both TLR2 and ANXA5.  Discussion: Tlr2 , Anxa5 , and Grin2a can serve as candidate multi-omics signature molecules of CCH in the mouse brain, with consistent alterations at the transcriptomic, proteomic, and tissue levels.
SN  - 1664-2295
ER  -