{"doi":"10.3390/ijms24098091","title":"Exploratory Transcriptomic Profiling Reveals the Role of Gut Microbiota in Vascular Dementia","abstract":"Stroke is the second most common cause of cognitive impairment and dementia. Vascular dementia (VaD), a cognitive impairment following a stroke, is common and significantly impacts the quality of life. We recently demonstrated via gut microbe transplant studies that the gut microbe-dependent trimethylamine-N-oxide (TMAO) pathway impacts stroke severity, both infarct size and long-term cognitive outcomes. However, the molecular mechanisms that underly the role of the microbiome in VaD have not been explored in depth. To address this issue, we performed a comprehensive RNA-sequencing analysis to identify differentially expressed (DE) genes in the ischemic cerebral cortex of mouse brains at pre-stroke and post-stroke day 1 and day 3. A total of 4016, 3752 and 7861 DE genes were identified at pre-stroke and post-stroke day 1 and day 3, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated pathways of neurodegeneration in multiple diseases, chemokine signaling, calcium signaling, and IL-17 signaling as the key enriched pathways. Inflammatory response genes interleukin-1 beta (Il-1β), chemokines (C–X–C motif chemokine ligand 10 (Cxcl10), chemokine ligand 2 (Ccl2)), and immune system genes (S100 calcium binding protein 8 (S100a8), lipocalin-2 (Lcn2)) were among the most significantly upregulated genes. Hypocretin neuropeptide precursor (Hcrt), a neuropeptide, and transcription factors such as neuronal PAS domain protein 4 (Npas4), GATA binding protein 3 (Gata3), and paired box 7 (Pax7) were among the most significantly downregulated genes. In conclusion, our results indicate that higher plasma TMAO levels induce differential mRNA expression profiles in the ischemic brain tissue in our pre-clinical stroke model, and the predicted pathways provide the molecular basis for regulating the TMAO-enhanced neuroinflammatory response in the brain.","journal":"International Journal of Molecular Sciences","year":2023,"id":338339,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":877625,"name":"Geneva LaForce","orcid":"0000-0002-5046-5194","position":1,"is_corresponding":false},{"id":1070751,"name":"Deepthi P. Mallela","orcid":"0000-0002-2703-4353","position":2,"is_corresponding":false},{"id":108882,"name":"Prasenjit Prasad Saha","orcid":"0000-0003-4679-2368","position":3,"is_corresponding":false},{"id":346396,"name":"Jennifer A. Buffa","orcid":null,"position":4,"is_corresponding":false},{"id":405031,"name":"Xinmin S. Li","orcid":"0000-0003-4946-4271","position":5,"is_corresponding":false},{"id":263517,"name":"Naseer Sangwan","orcid":"0000-0002-2407-769X","position":6,"is_corresponding":false},{"id":894464,"name":"Kasia Gustaw Rothenberg","orcid":null,"position":7,"is_corresponding":false},{"id":108884,"name":"Weifei Zhu","orcid":"0000-0003-4355-134X","position":8,"is_corresponding":false},{"id":1070750,"name":"Navdeep Kaur","orcid":"0000-0003-4583-1687","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T01:10:35.973121Z","pmid":"37175797","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}