{"id":"e34a672a-c802-5d00-9d5d-c4a37b53f14c","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-acetate-learning-programs","predicate":"increases","statement":"In isolated primary hippocampal neurons ex vivo, extracellular acetate induced transcriptional programs related to learning and memory which were sensitive to ACSS2 inhibition, and alcohol-related associative learning was shown to require ACSS2 in vivo.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"cc14e43e-7195-5d24-97e6-d99f1b390125","mechanism_event_label":"Acetate outside the neuron switches on the genes of learning, and blocking the enzyme that uses it blocks the learning too.","subject":{"id":"e366e758-1fb0-5573-aed1-34f6df874ac7","slug":"acetate","display_name":"Acetate","entity_type_key":"small_molecule"},"object":{"id":"f90fcf54-3870-57b9-bc75-a818f2896862","slug":"learning-and-memory-transcription","display_name":"Transcriptional programs related to learning and memory in hippocampal neurons","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cc14e43e-7195-5d24-97e6-d99f1b390125","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-acetate-learning-programs-event","event_type":"biochemical_relationship","label":"Acetate outside the neuron switches on the genes of learning, and blocking the enzyme that uses it blocks the learning too.","description":"In isolated primary hippocampal neurons ex vivo, extracellular acetate induced transcriptional programs related to learning and memory which were sensitive to ACSS2 inhibition, and alcohol-related associative learning was shown to require ACSS2 in vivo.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"64044850-0d45-5593-9a51-fa645679f99b","slug":"acss2","display_name":"Human acetyl-CoA synthetase 2 / ACSS2","entity_type_key":"protein"},"role":"required_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"daa98f63-3337-57af-af5f-e28b07473d39","slug":"associative-learning","display_name":"Alcohol-related associative learning","entity_type_key":"cellular_process"},"role":"behavioural_readout","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e366e758-1fb0-5573-aed1-34f6df874ac7","slug":"acetate","display_name":"Acetate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f90fcf54-3870-57b9-bc75-a818f2896862","slug":"learning-and-memory-transcription","display_name":"Transcriptional programs related to learning and memory in hippocampal neurons","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/acetate-research/31645761.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a7a812a410fd8be3bad8512ab46d4b8a7fd3329d1552ee30965b66860eeb2b2f\", \"start_char\": 0, \"end_char\": 1646, \"text_sha256\": \"a7a812a410fd8be3bad8512ab46d4b8a7fd3329d1552ee30965b66860eeb2b2f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"In vivo stable-isotope labelling in mice, with primary hippocampal neurons and behavioural testing","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Labelled alcohol or heavy-labelled acetate administered in vivo, with ACSS2 inhibition and deletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Isotope labelling traces the actual carbon atoms onto histones, which is stronger than correlating acetylation with exposure. A mouse study; the fetal result is a single reported exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetic-acid","display_name":"Acetic acid","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Acetate outside the neuron switches on the genes of learning, and blocking the enzyme that uses it blocks the learning too.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[acetate-p31645761] Alcohol metabolism contributes to brain histone acetylation. (2019). https://pubmed.ncbi.nlm.nih.gov/31645761/ DOI: 10.1038/s41586-019-1700-7","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Brain and gestating fetus","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"21f9dff0-bab3-5cdc-adf7-dd2433a67c7b","evidence_kind":"source_excerpt","locator":"Lines 641-652","start_line":641,"end_line":652,"excerpt":"### acetate-acetate-learning-programs\nIn isolated primary hippocampal neurons ex vivo, extracellular acetate induced transcriptional programs related to learning and memory which were sensitive to ACSS2 inhibition, and alcohol-related associative learning was shown to require ACSS2 in vivo.\nCondition category: normal\nnutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion.\nplain_language: Acetate outside the neuron switches on the genes of learning, and blocking the enzyme that uses it blocks the learning too.\norganism: Mouse\ntissue_or_cell_type: Brain and gestating fetus\nexperimental_model: In vivo stable-isotope labelling in mice, with primary hippocampal neurons and behavioural testing\nlimitations: Isotope labelling traces the actual carbon atoms onto histones, which is stronger than correlating acetylation with exposure. A mouse study; the fetal result is a single reported exposure.\nexposure: Labelled alcohol or heavy-labelled acetate administered in vivo, with ACSS2 inhibition and deletion\nevidence_span: {\"source_cache\": \"artifacts/acetate-research/31645761.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a7a812a410fd8be3bad8512ab46d4b8a7fd3329d1552ee30965b66860eeb2b2f\", \"start_char\": 0, \"end_char\": 1646, \"text_sha256\": \"a7a812a410fd8be3bad8512ab46d4b8a7fd3329d1552ee30965b66860eeb2b2f\"}\n[acetate-p31645761] Alcohol metabolism contributes to brain histone acetylation. (2019). https://pubmed.ncbi.nlm.nih.gov/31645761/ DOI: 10.1038/s41586-019-1700-7","model_system":"In vivo stable-isotope labelling in mice, with primary hippocampal neurons and behavioural testing","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [acetate-p31645761] Alcohol metabolism contributes to brain histone acetylation. (2019). https://pubmed.ncbi.nlm.nih.gov/31645761/ DOI: 10.1038/s41586-019-1700-7","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"8356baaf-173c-5549-80cd-bbbb2007ffb5","stable_key":"import-b26c9d01-98fd-50d3-8f39-44db46961ee5","title":"Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"1441d249b16db25c0d488407e5cc881222acffc2f16af88cb3197d9d5697bccc","revision_id":"9bfeb605-f589-5e99-84b9-e56968a3bc1f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}