ID: hyp-SDA-2026-04-08-gap-pubmed-20260406-0
Hypothesis
ADCY8-cAMP Memory Consolidation Enhancer
ADCY8 variants that increase adenylyl cyclase activity could enhance cAMP-dependent memory consolidation specifically for spatial navigation tasks.
memory and navigation
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 1 oppose
✓ All Quality Gates Passed
🧪 Overview
ADCY8 variants that increase adenylyl cyclase activity could enhance cAMP-dependent memory consolidation specifically for spatial navigation tasks. Pharmacological activation of ADCY8 or downstream cAMP signaling could improve long-term spatial memory formation in neurodegenerative diseases affecting navigation abilities.
🧬 Mechanism
🔗 Mechanism from KG for ADCY8
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:#000⚖️ Evidence
⚖️ Evidence Matrix5 supports0 contradicts
Supports
Adcy8 deficiency contributes to impaired lipolysis and an increased prevalence of obesity in mice.
Supports
FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells.
Supports
Ca(2+)-stimulated ADCY1 and ADCY8 regulate distinct aspects of synaptic and cognitive flexibility.
Supports
Multilevel control of glucose homeostasis by adenylyl cyclase 8.
Supports
Polymorphism in ovine ADCY8 gene and its association with residual feed intake in Hu sheep.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — ADCY8
No curated PDB or AlphaFold mapping for ADCY8 yet. Search RCSB →
💉 Clinical Trials
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.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
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Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0535
Events (7d)
0
Price History
▲6.0%💾 Resource Usage
LLM Tokens
7,012
$0.0421
Total Cost
$0.0421
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF APP/PS1 transgenic mice (a model of Alzheimer's disease amyloid pathology) are administered a selective pharmacological ADCY8 activator or Forskolin analog 30 minutes before spatial navigation trai | Mean latency to find the hidden platform during the 24-hour probe trial will be ≤60% of vehicle-treated control latency, with ≥50% increase in platform zone cro | — no observation — | pending | 0.55 |
| IF humans carrying gain-of-function ADCY8 variants (non-synonymous SNPs associated with increased adenylyl cyclase activity) are compared to age- and sex-matched controls in a standardized spatial nav | Mean spatial memory consolidation score will be ≥20% higher in ADCY8 gain-of-function variant carriers compared to matched controls, with reduced latency to pla | — no observation — | pending | 0.65 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF humans carrying gain-of-function ADCY8 variants (non-synonymous SNPs associated with increased adenylyl cyclase activity) are compared to age- and sex-matched controls in a standardized spatial navigation memory paradigm THEN they will demonstrate significantly higher spatial memory consolidation
Predicted outcome: Mean spatial memory consolidation score will be ≥20% higher in ADCY8 gain-of-function variant carriers compared to matched controls, with reduced late
Falsification: No statistically significant difference (p > 0.05) or worse performance in spatial memory consolidation scores between ADCY8 variant carriers and controls, or effect size < 0.3 Cohen's d.
pendingconf 55%
IF APP/PS1 transgenic mice (a model of Alzheimer's disease amyloid pathology) are administered a selective pharmacological ADCY8 activator or Forskolin analog 30 minutes before spatial navigation training in the Morris Water Maze, THEN these mice will demonstrate significantly improved long-term spa
Predicted outcome: Mean latency to find the hidden platform during the 24-hour probe trial will be ≤60% of vehicle-treated control latency, with ≥50% increase in platfor
Falsification: No statistically significant improvement in spatial memory retention (probe trial performance equivalent to or worse than vehicle controls, p > 0.05), or evidence of seizures/locomotor impairment conf
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesis
| source | v1_phase_c_backfill |
| origin_type | debate_synthesis |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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