{"artifact":{"id":"experiment-exp-wiki-experiments-synaptic-mitochondrial-resilience-pd","artifact_type":"experiment","entity_ids":null,"title":"Synaptic Mitochondrial Resilience Enhancement for Parkinson's Disease","quality_score":0.675,"created_by":"crosslink-v2","provenance_chain":null,"content_hash":null,"metadata":{"source":{"type":"manual","source_name":"wiki","extracted_by":"backfill_v1","extraction_date":"2026-04-16T01:00:16.902317Z"},"summary":"# Synaptic Mitochondrial Resilience Enhancement for Parkinson's Disease\n## Background and Rationale\nParkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra, with synaptic terminals in the striatum being the earliest sites of pathology. Mitochondrial dysfunction is a central mechanism in PD pathogenesis, contributing to synaptic energy deficits and oxidative stress that precipitate neurodegeneration. This validation study tests the the","entities":{"genes":["ATP"],"diseases":["Parkinson's Disease"]},"model_system":"human","_schema_version":1,"experiment_type":"validation","primary_outcome":"Preservation of TH+ striatal fiber density with PGC-1alpha overexpression vs. controls","methodology_notes":"Phase 1 (Weeks 1-4): Stereotaxic injection of AAV9-PGC1alpha or AAV9-GFP control vectors (1x10^12 vg/ml, 2μl) into substantia nigra of 8-week-old male C57BL/6 mice (n=30/group). Coordinates: AP -3.1mm, ML ±1.2mm, DV -4.2mm from bregma. Phase 2 (Weeks 5-11): Recovery and transgene expression period with weekly weight monitoring. Phase 3 (Week 12): Unilateral 6-OHDA lesion (8μg/2μl in 0.02% ascorbic acid/saline) into medial forebrain bundle (AP -0.7mm, ML +1.2mm, DV -7.8mm). Desipramine (25mg/kg IP) administered 30 minutes prior to protect noradrenergic terminals. Phase 4 (Weeks 13-16): Behavioral testing including apomorphine-induced rotation (0.5mg/kg SC, rotations counted for 60 minutes) and cylinder test for forelimb asymmetry (100 contacts scored). Phase 5 (Weeks 17-24): Terminal assessments with tissue collection for HPLC analysis of striatal dopamine/metabolites, immunohistochemical quantification of TH+ fibers using unbiased stereology, transmission electron microscopy for synapt","replication_status":"single_study","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.902323","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID available)","extraction_confidence":0.4}},"created_at":"2026-04-02T10:01:41.825940-07:00","updated_at":"2026-04-16T01:00:16-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":"2026-04-02T10:01:41.825940-07:00","citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":"ok","contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"d5ca932e-b5c3-4eab-b951-13d83c1363c0","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"crosslink-v2"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[{"target_artifact_id":"wiki-genes-tfam","link_type":"related","strength":0.63,"evidence":"Reverse: 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