{"doi":"10.3390/metabo14120699","title":"Effects of Acute Stress on Metabolic Interactions Related to the Tricarboxylic Acid (TCA) Cycle in the Left Hippocampus of Mice","abstract":"<jats:p>Background/objectives: The acute stress response affects brain metabolites closely linked to the tricarboxylic acid (TCA) cycle. This response involves time-dependent changes in hormones and neurotransmitters, which contribute to resilience and the ability to adapt to acute stress while maintaining homeostasis. This physiological mechanism of metabolic dynamics, combined with time-series analysis, has prompted the development of new methods to observe the relationship between TCA cycle-related brain metabolites. This study aimed to observe the acute stress response through metabolic interactions using time-series proton magnetic resonance spectroscopy (1H-MRS) in the left hippocampus of mice. Methods: In this study, 4-week-old male C57BL/6N mice (n = 24) were divided into control (n = 12) and acute stress groups (n = 12). Acute stress was induced through a 2 h restraint protocol. Time-series 1H-MRS data were obtained on the left hippocampus of both groups using a 9.4 T 1H-MRS scanner. Time-series MRS data were quantified using LCModel, and significant metabolic interactions were identified through Spearman correlation analysis, a one-tailed sign test, and false discovery rate correction. Results: No significant metabolic correlation coefficient was observed in the control group. However, in the acute stress group, glutathione (GSH) and N-acetyl aspartate (NAA) showed a significant positive correlation over time, with a high correlation coefficient exceeding 0.5. Conclusions: Temporal measurement of GSH and NAA, combined with correlation analysis, offers a comprehensive understanding for the metabolic dynamics during acute stress. This approach emphasizes their distinct roles and interdependence in the progression of oxidative stress, mitochondrial function, and the maintenance of physiological homeostasis.</jats:p>","journal":"Metabolites","year":2024,"id":600066,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1418778,"name":"Yoon Ho Hwang","orcid":"0000-0003-0636-7084","position":1,"is_corresponding":false},{"id":1538179,"name":"Jehyeong Yeon","orcid":null,"position":2,"is_corresponding":false},{"id":1398718,"name":"Hyeon-Man Baek","orcid":null,"position":3,"is_corresponding":false},{"id":1538180,"name":"Dong Youn Kim","orcid":null,"position":4,"is_corresponding":false},{"id":1538181,"name":"Bong Soo Han","orcid":null,"position":5,"is_corresponding":false},{"id":364773,"name":"Chang‐Soo Yun","orcid":"0000-0002-2814-3797","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Effects of Acute Stress on Metabolic Interactions Related to the Tricarboxylic Acid (TCA) Cycle in the Left Hippocampus of Mice","abstract":"<jats:p>Background/objectives: The acute stress response affects brain metabolites closely linked to the tricarboxylic acid (TCA) cycle. This response involves time-dependent changes in hormones and neurotransmitters, which contribute to resilience and the ability to adapt to acute stress while maintaining homeostasis. This physiological mechanism of metabolic dynamics, combined with time-series analysis, has prompted the development of new methods to observe the relationship between TCA cycle-related brain metabolites. This study aimed to observe the acute stress response through metabolic interactions using time-series proton magnetic resonance spectroscopy (1H-MRS) in the left hippocampus of mice. Methods: In this study, 4-week-old male C57BL/6N mice (n = 24) were divided into control (n = 12) and acute stress groups (n = 12). Acute stress was induced through a 2 h restraint protocol. Time-series 1H-MRS data were obtained on the left hippocampus of both groups using a 9.4 T 1H-MRS scanner. Time-series MRS data were quantified using LCModel, and significant metabolic interactions were identified through Spearman correlation analysis, a one-tailed sign test, and false discovery rate correction. Results: No significant metabolic correlation coefficient was observed in the control group. However, in the acute stress group, glutathione (GSH) and N-acetyl aspartate (NAA) showed a significant positive correlation over time, with a high correlation coefficient exceeding 0.5. Conclusions: Temporal measurement of GSH and NAA, combined with correlation analysis, offers a comprehensive understanding for the metabolic dynamics during acute stress. This approach emphasizes their distinct roles and interdependence in the progression of oxidative stress, mitochondrial function, and the maintenance of physiological homeostasis.</jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39728480","pmcid":"PMC11678911","openalex_id":"https://openalex.org/W4405291440","authors":[],"funders":[{"funder_name":"National Research Foundation of Korea (NRF) funded by the Ministry of Education","grant_id":"2020R1A2C1015179","title":null},{"funder_name":"Korea Institute of Energy Technology Evaluation and Planning (KETEP) and the Ministry of Trade, Industry & Energy (MOTIE) of the Republic of Korea","grant_id":"20214000000070","title":null}],"total_grants":2,"fwci":0.5351,"citation_percentile":0.67409568,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2218-1989/14/12/699/pdf?version=1733907350","host_type":"journal"},{"url":"https://www.mdpi.com/2218-1989/14/12/699/pdf?version=1733907350","host_type":"publisher"},{"url":"https://www.mdpi.com/2218-1989/14/12/699/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/metabo14120699","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39728480","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11678911","host_type":"repository"},{"url":"https://doaj.org/article/b5f09476acac4db0a0f6e0947c595ee9","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11678911/pdf/metabolites-14-00699.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11678911","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11678911?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Advanced MRI Techniques and Applications","Stress Responses and Cortisol","Neuroscience and Neuropharmacology Research"],"mesh_terms":[],"keywords":["Citric acid cycle","Tricarboxylic acid","Hippocampus","Chemistry","Internal medicine","Metabolism","Endocrinology","Biology","Biochemistry","Medicine","Proton Magnetic Resonance Spectroscopy","Acute Stress Response","Metabolites Interaction"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T12:08:37.495893Z","pmid":null,"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":[]}