Integrated transcriptomic and proteomic profiling reveals C3-associated hippocampal neuroimmune remodeling in sodium bicarbonate-treated sepsis-associated encephalopathy
4 affiliations
- 1The First People's Hospital of Chenzhou, Medical Education Center of Jinan University
- 2The Affiliated Suzhou Hospital of Nanjing Medical University
- 3The Second Affiliated Hospital of Nanjing Medical University
- 4The First Affiliated Hospital of Jinan University
Abstract
Background: Sepsis-associated encephalopathy (SAE) is a neurological complication of sepsis characterized by cognitive impairment and persistent brain dysfunction. Although neuroinflammation and glial activation contribute to SAE pathogenesis, the molecular alterations underlying hippocampal neuroimmune dysfunction remain incompletely understood. The potential role of NaHCO₃ in SAE-associated neurological dysfunction remains unclear.
Methods: An LPS-induced mouse model of SAE was established to investigate the effects of NaHCO₃ administration. Survival and cognitive function were evaluated using survival analysis, novel object recognition, open-field, and Y-maze tests. Hippocampal transcriptomic and proteomic profiling was performed, followed by cross-omics integration. Candidate molecules were further assessed by qRT-PCR, Western blotting, and immunofluorescence.
Results: NaHCO₃ treatment improved survival and alleviated cognitive deficits in SAE mice. Transcriptomic and proteomic profiling revealed extensive hippocampal molecular alterations, with functional enrichment highlighting immune- and inflammation-related processes and pathways. Three-group cross-omics analysis identified 18 candidates meeting an FDR < 0.05 at both omics levels and showing a concordant SAE-associated increase followed by a decrease after NaHCO₃ treatment. Among these candidates, C3 was prioritized based on its cross-omics expression pattern and neuroimmune relevance. qRT-PCR and Western blot analyses supported increased hippocampal C3 expression during SAE and its responsiveness to NaHCO₃ treatment. Immunofluorescence analysis revealed increased spatial association between C3 and GFAP-positive astrocytic structures during SAE, which was attenuated following NaHCO₃ treatment.
Conclusion: NaHCO₃ treatment was associated with improved neurological outcomes and altered hippocampal molecular profiles in LPS-induced SAE. Cross-omics analysis identified C3 among candidate molecules associated with SAE and NaHCO₃ responsiveness. The increased C3–GFAP spatial association suggests that complement-associated alterations accompany astrocytic responses during SAE. The causal role of C3 and the mechanisms underlying the effects of NaHCO₃ require further investigation.
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BibTeX
@article{deng2026integrated,
title = {{Integrated transcriptomic and proteomic profiling reveals C3-associated hippocampal neuroimmune remodeling in sodium bicarbonate-treated sepsis-associated encephalopathy}},
author = {Housheng Deng and Hua Ling and Lie Liu and Qiuli He and Hao Wang and Zhiming Zhang},
journal = {Frontiers in Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnins.2026.1954272},
url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1954272/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated transcriptomic and proteomic profiling reveals C3-associated hippocampal neuroimmune remodeling in sodium bicarbonate-treated sepsis-associated encephalopathy
AU - Housheng Deng
AU - Hua Ling
AU - Lie Liu
AU - Qiuli He
AU - Hao Wang
AU - Zhiming Zhang
PY - 2026
DA - 2026/10/07
JO - Frontiers in Neuroscience
DO - 10.3389/fnins.2026.1954272
UR - https://www.frontiersin.org/articles/10.3389/fnins.2026.1954272/full
AB - Background: Sepsis-associated encephalopathy (SAE) is a neurological complication of sepsis characterized by cognitive impairment and persistent brain dysfunction. Although neuroinflammation and glial activation contribute to SAE pathogenesis, the molecular alterations underlying hippocampal neuroimmune dysfunction remain incompletely understood. The potential role of NaHCO₃ in SAE-associated neurological dysfunction remains unclear. Methods: An LPS-induced mouse model of SAE was established to investigate the effects of NaHCO₃ administration. Survival and cognitive function were evaluated using survival analysis, novel object recognition, open-field, and Y-maze tests. Hippocampal transcriptomic and proteomic profiling was performed, followed by cross-omics integration. Candidate molecules were further assessed by qRT-PCR, Western blotting, and immunofluorescence. Results: NaHCO₃ treatment improved survival and alleviated cognitive deficits in SAE mice. Transcriptomic and proteomic profiling revealed extensive hippocampal molecular alterations, with functional enrichment highlighting immune- and inflammation-related processes and pathways. Three-group cross-omics analysis identified 18 candidates meeting an FDR < 0.05 at both omics levels and showing a concordant SAE-associated increase followed by a decrease after NaHCO₃ treatment. Among these candidates, C3 was prioritized based on its cross-omics expression pattern and neuroimmune relevance. qRT-PCR and Western blot analyses supported increased hippocampal C3 expression during SAE and its responsiveness to NaHCO₃ treatment. Immunofluorescence analysis revealed increased spatial association between C3 and GFAP-positive astrocytic structures during SAE, which was attenuated following NaHCO₃ treatment. Conclusion: NaHCO₃ treatment was associated with improved neurological outcomes and altered hippocampal molecular profiles in LPS-induced SAE. Cross-omics analysis identified C3 among candidate molecules associated with SAE and NaHCO₃ responsiveness. The increased C3–GFAP spatial association suggests that complement-associated alterations accompany astrocytic responses during SAE. The causal role of C3 and the mechanisms underlying the effects of NaHCO₃ require further investigation.
SN - 1662-453X
SN - 1662-4548
ER -