TMT Screening and Bioinformatic Analysis of Differentially Expressed Proteins of Hippocampus in AD Rat Model
- VernacularTitle:AD大鼠模型海马差异表达蛋白的TMT筛查与生信分析
- Author:
Chao KE
1
;
Shengtao SHAN
1
;
Yan TAN
1
;
Yang CAO
1
;
Zhengrong XIE
1
;
Jiang PAN
1
;
Wei ZHANG
1
Author Information
- Publication Type:Journal Article
- Keywords: Alzheimer's disease; Proteomics; Beta amyloid protein; Glutamate synapses; Biotechnology analysis
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(11):3350-3361
- CountryChina
- Language:Chinese
- Abstract: Objective To analyze differentially expressed proteins(DEPs)in the hippocampal tissue of an amyloid-beta 1-42(Aβ1-42)-induced Alzheimer's disease(AD)rat model using Tandem mass tag(TMT)-based quantitative proteomics,followed by bioinformatic analysis to explore potential AD mechanisms.Methods Twelve male Sprague-Dawley(SD)rats were randomly assigned to a control group(n=6)and a model group(n=6).The AD model was established by bilateral hippocampal injection of Aβ1-42 in the model group,while the control group received an equivalent volume of saline.Cognitive function was assessed using the novel object recognition test,and hippocampal Aβ deposition was detected by immunofluorescence.DEPs were identified using TMT-based proteomics and subsequently analyzed via Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interaction(PPI)network analysis.Key DEPs were validated using parallel reaction monitoring(PRM)technology.Results The model group exhibited a significantly lower novel object recognition index(P<0.01)and significantly increased hippocampal Aβ deposition(P<0.01)compared to the control group.Proteomic analysis identified 183 DEPs(87 upregulated,96 downregulated).GO analysis revealed that DEPs were primarily enriched in processes such as amyloid-beta binding and ion transmembrane transport.KEGG analysis indicated significant enrichment in 42 pathways,including dopaminergic synapse,glutamatergic synapse,cholinergic synapse,and long-term potentiation.Ten core DEPs were identified from the PPI network,and PRM validation confirmed expression trends consistent with the TMT results.Conclusion Aβ1-42-induced AD involves the synergistic action of multiple targets,biological processes,and pathways.The activation of glutamatergic and dopaminergic synaptic signaling pathways,mediated by core DEPs(e.g.,Th、D1、VGLUT2、GluN2A、GluA1、GluA3、Shank1、DARPP-32、PKC-δ、PKC-α、PKA C-β、CaMKⅡα、PTK2B),likely represents a key molecular mechanism in this AD model,providing a basis for identifying potential therapeutic targets.
