{"id":"41126d3d-8cd0-5287-9f70-cbb6a698a13b","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:thiamine-def-conditioned-medium-uptake","predicate":"antagonist-assisted-depletion-generates-medium-that-reduces","statement":"Medium from depleted astrocytes reduced glutamate uptake in naive recipient astrocytes by over 70% after 24 hours.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"20ccb9c3-d583-5b66-8b52-8c2d3a10241b","mechanism_event_label":"The culture environment from depleted cells transferred a defect in glutamate removal.","subject":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"object":{"id":"cc1a4f41-3c78-5d2d-a9d8-e508dae25ba9","slug":"astrocyte-glutamate-uptake","display_name":"Astrocyte glutamate uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"20ccb9c3-d583-5b66-8b52-8c2d3a10241b","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:thiamine-def-conditioned-medium-uptake-event","event_type":"biochemical_relationship","label":"The culture environment from depleted cells transferred a defect in glutamate removal.","description":"Medium from depleted astrocytes reduced glutamate uptake in naive recipient astrocytes by over 70% after 24 hours.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7da684a4-2641-5bc6-93ae-8c6aa384e487","slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"},"role":"uptake substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"75a7f374-5ae9-5565-9f52-388e627bb492","slug":"pyrithiamine","display_name":"Pyrithiamine","entity_type_key":"small_molecule"},"role":"donor-culture antagonist","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5f5f1cd4-d807-537b-b553-0f8808f59cae","slug":"rat-slc1a2-glt1b","display_name":"Rat GLT-1b transporter isoform","entity_type_key":"protein"},"role":"measured transporter isoform in the same study","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"cc1a4f41-3c78-5d2d-a9d8-e508dae25ba9","slug":"astrocyte-glutamate-uptake","display_name":"Astrocyte glutamate uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_location","value_text":"Results snippet: Effects of TD conditioned media on glutamate transport; Figure 1A","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"reduced by over 70% after 24 h","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Newborn-rat astrocytes differentiated with dibutyryl cAMP; thiamine-free DMEM with 5% horse serum plus 10 micromolar pyrithiamine; conditioned-medium transfer and inflammatory-pathway inhibitors.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Thiamine-free medium plus pyrithiamine in cultured newborn-rat astrocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Conditioned medium is a mixture; this comparison alone cannot identify a secreted mediator or exclude carried-over medium components.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Thiamine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Rattus norvegicus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The culture environment from depleted cells transferred a defect in glutamate removal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[jhala-2014-astrocyte-inflammatory-signaling] Thiamine deficiency results in release of soluble factors that disrupt mitochondrial membrane potential and downregulate the glutamate transporter splice-variant GLT-1b in cultured astrocytes. 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