The memory-based navigation differences associated with ADCY8 may involve epigenetic programming during critical developmental windows. Therapeutic epigenetic reprogramming of ADCY8 expression could restore spatial memory capabilities by reactivating juvenile-like plasticity in navigation circuits.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
ADCY8["ADCY8"] -->|produces| cAMP["cAMP"]
ADCY8_1["ADCY8"] -->|modulates| spatial_navigation["spatial_navigation"]
ADCY8_2["ADCY8"] -->|activates| PKA_CREB_signaling_cascad["PKA-CREB signaling cascade"]
ADCY8_3["ADCY8"] -->|regulates| long_term_spatial_memory_["long-term spatial memory formation"]
ADCY8_4["ADCY8"] -->|activates| cAMP_signaling["cAMP signaling"]
ADCY8_5["ADCY8"] -->|activates| PKA["PKA"]
ADCY8_6["ADCY8"] -->|regulates| spatial_memory_formation["spatial memory formation"]
ADCY8_7["ADCY8"] -->|regulates| hippocampus["hippocampus"]
ADCY8_8["ADCY8"] -->|causes| long_term_spatial_memory__9["long_term_spatial_memory_formation"]
ADCY8_10["ADCY8"] -->|modulates| epigenetic_programming["epigenetic_programming"]
ADCY8_11["ADCY8"] -->|protective against| navigation_disorders["navigation_disorders"]
ADCY8_12["ADCY8"] -->|modulates| synaptic_plasticity["synaptic_plasticity"]
ADCY8_13["ADCY8"] -->|enhances| adenylyl_cyclase_activity["adenylyl_cyclase_activity"]
ADCY8_14["ADCY8"] -->|couples with| circadian_rhythms["circadian_rhythms"]
ADCY8_variants["ADCY8 variants"] -->|enhances| cAMP_dependent_memory_con["cAMP-dependent memory consolidation"]
style ADCY8 fill:#ce93d8,stroke:#333,color:#000
style cAMP fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_1 fill:#ce93d8,stroke:#333,color:#000
style spatial_navigation fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_2 fill:#ce93d8,stroke:#333,color:#000
style PKA_CREB_signaling_cascad fill:#81c784,stroke:#333,color:#000
style ADCY8_3 fill:#ce93d8,stroke:#333,color:#000
style long_term_spatial_memory_ fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_4 fill:#ce93d8,stroke:#333,color:#000
style cAMP_signaling fill:#81c784,stroke:#333,color:#000
style ADCY8_5 fill:#ce93d8,stroke:#333,color:#000
style PKA fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_6 fill:#ce93d8,stroke:#333,color:#000
style spatial_memory_formation fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_7 fill:#ce93d8,stroke:#333,color:#000
style hippocampus fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_8 fill:#ce93d8,stroke:#333,color:#000
style long_term_spatial_memory__9 fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_10 fill:#ce93d8,stroke:#333,color:#000
style epigenetic_programming fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_11 fill:#ce93d8,stroke:#333,color:#000
style navigation_disorders fill:#ef5350,stroke:#333,color:#000
style ADCY8_12 fill:#ce93d8,stroke:#333,color:#000
style synaptic_plasticity fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_13 fill:#ce93d8,stroke:#333,color:#000
style adenylyl_cyclase_activity fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_14 fill:#ce93d8,stroke:#333,color:#000
style circadian_rhythms fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_variants fill:#ce93d8,stroke:#333,color:#000
style cAMP_dependent_memory_con fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for ADCY8 yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for ADCY8.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we selectively demethylate the ADCY8 gene promoter region during early postnatal development (P7-P21) in C57BL/6J mice using CRISPR-dCas9-TET1 fusion protein delivered via AAV9, THEN these mice wil | Reduced escape latency (≤20 seconds vs. ≥28 seconds in controls) and increased platform crossing in probe trial. | — no observation — | pending | 0.45 |
| IF we administer systemic HDAC inhibitor (SAHA, 50mg/kg, i.p., 14 days) to aged C57BL/6J mice (18-20 months) with documented navigation deficits, THEN spatial memory will be restored to young adult le | Escape latency reduction to ≤22 seconds (vs. ≥32 seconds in vehicle) and ADCY8 promoter methylation reduction to ≤25% (vs. ≥50% in aged controls). | — no observation — | pending | 0.38 |