{"id":"b1c93ee7-f10f-57cf-8168-ace7f3c20cf0","stable_key":"9a47f338-d127-5e4d-abf6-e99056833a69:d-aspartate-olanzapine-mouse-dependence","predicate":"increases_tested","statement":"Four weeks of olanzapine at 5 mg/kg/day intraperitoneally increased prefrontal extracellular D-aspartate and glutamate in wild-type mice; the increments were absent in Ddo-knockout mice.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"931d5853-e6ae-5661-b20b-b54890d6e937","mechanism_event_label":"Removing the enzyme removed this drug-associated increment in the mouse experiment.","subject":{"id":"e83902e5-cd44-5de2-b790-abf19033d265","slug":"olanzapine","display_name":"Olanzapine","entity_type_key":"small_molecule"},"object":{"id":"1611a808-0ccd-537c-b4e6-7f7e6fea3456","slug":"mouse-pfc-extracellular-d-aspartate","display_name":"Extracellular D-aspartate in mouse prefrontal cortex","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"931d5853-e6ae-5661-b20b-b54890d6e937","stable_key":"9a47f338-d127-5e4d-abf6-e99056833a69:d-aspartate-olanzapine-mouse-dependence-event","event_type":"observed_relationship","label":"Removing the enzyme removed this drug-associated increment in the mouse experiment.","description":"Four weeks of olanzapine at 5 mg/kg/day intraperitoneally increased prefrontal extracellular D-aspartate and glutamate in wild-type mice; the increments were absent in Ddo-knockout mice.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e83902e5-cd44-5de2-b790-abf19033d265","slug":"olanzapine","display_name":"Olanzapine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1611a808-0ccd-537c-b4e6-7f7e6fea3456","slug":"mouse-pfc-extracellular-d-aspartate","display_name":"Extracellular D-aspartate in mouse prefrontal cortex","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b3404670-6db1-517f-b9a0-27ecfaac558b","slug":"d-aspartate","display_name":"D-Aspartate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f3fc3b2e-7748-5a0a-a936-94c47f68a6d2","slug":"mouse-ddo","display_name":"Mouse D-aspartate oxidase / Ddo","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"7da684a4-2641-5bc6-93ae-8c6aa384e487","slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"2131891d-599e-5f0d-99f2-641cbbae52a7","slug":"clozapine","display_name":"Clozapine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse microdialysis 24 hours after the final injection.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Knockouts already differ at baseline. This does not prove the pathway mediates clinical antipsychotic efficacy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"d-aspartate","display_name":"D-Aspartate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Removing the enzyme removed this drug-associated increment in the mouse experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"912d992b-adce-5e21-a66b-8b4ec48936f4","evidence_kind":"source_excerpt","locator":"Lines 280-286","start_line":280,"end_line":286,"excerpt":"## d-aspartate-olanzapine-mouse-dependence\nRemoving the enzyme removed this drug-associated increment in the mouse experiment.\nFour weeks of olanzapine at 5 mg/kg/day intraperitoneally increased prefrontal extracellular D-aspartate and glutamate in wild-type mice; the increments were absent in Ddo-knockout mice.\nModel: Mouse microdialysis 24 hours after the final injection.\nLimitations: Knockouts already differ at baseline. This does not prove the pathway mediates clinical antipsychotic efficacy.\nEvidence access: Primary full text\nOlanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288","model_system":"Mouse microdialysis 24 hours after the final injection.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3751103e-e256-5615-b24f-39cc76ccfb47","stable_key":"import-9a47f338-d127-5e4d-abf6-e99056833a69","title":"D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"0a86a1008edb8a69dcc79409e76e3fd5ce59b0747be8cae8f21e43f871e76248","revision_id":"a1de4b66-263d-5452-8ed8-df853afba030","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}