🧫
Anti-miR-155 LNA Oligonucleotide Shifts Microglia to Homeostatic State in LPS-Challenged and 3xTg-AD Mice
active
experiment
Created: 2026-04-26T13:48:17
By: etl-v1-backfill
Quality:
50%
✓ SciDEX
ID: exp-proposal-07e6e64587d0
🧫 Experiment Protocol
In VivoneurodegenerationMIR155C57BL/6J LPS model (chronic i.p. 0.5 mg/kg weekly x 8 wk) and 12-month 3xTg-AD mice (n=10/group x 4 groups)proposed
Test whether intrathecal delivery of a locked-nucleic-acid anti-miR-155 (LNA-155) reduces the IFN-gamma/miR-155 feed-forward amplification, shifts microglia to homeostatic state, and improves memory in LPS-induced neuroinflammation model and aged 3xTg-AD mice.
PRIMARY OUTCOME
miR-155 level in cortical microglia reduced >=60%; IL-6/TNF-alpha in CSF reduced >=40%
EXPECTED OUTCOMES
LNA-155 will reduce microglial miR-155 >=60%, suppress IFN-gamma/IL-6 in CSF >=40%, increase SHIP1 protein >=2x, and restore Y-maze alternation to >=60% (vs ~45% LPS-vehicle).
SUCCESS CRITERIA
Primary: miR-155 qPCR >=60% reduction in microglia (p<0.01). Secondary: Y-maze spontaneous alternation >=60% for LNA-155 group.
PROTOCOL
1. Synthesise LNA-155 (5-T+G+T+A+G+C+A+T+T+A+A-3) or scramble-LNA. 2. Intrathecal implant osmotic pump (2 ug/day, 28-day release) at LPS day 14 or 3xTg-AD 12 months. 3. Endpoints at day 42 / 14 months: - miRNA-seq on FACS-sorted CD11b+ microglia (miR-155 readout) - Multiplex cytokine (CSF: IL-6, TNF-alpha, IFN-gamma, IL-10) - Microglia morphology (Iba1 IHC, ramification index) - Fear conditioning, Y-maze. 4. Primary: miR-155 by qRT-PCR; secondary: cytokine panel, Y-maze alternation.
LINKED HYPOTHESES
Source: task:a989715e-c687-4558-91ca-74fce1474bd2
🧫 Experiment Extras
ESTIMATED COST
$58,000
TIMELINE
14 months
PATHWAY
miR-155 -> SHIP1 suppression -> PI3K/NF-kB -> IFN-gamma production feedback loop
MARKET PRICE
$0.50
STATUS
proposed
Scoring Dimensions
Prediction Markets (1 direct, 0 via hypothesis — 1 total)
miR-155/Interferon-gamma Feedback Loop as a Reversible Molecular Switch for Protective MicYES 79% · Liq $100 · active▸Metadataorigin_type: v1_polymorphic_backfill
| origin_type | v1_polymorphic_backfill |
| source_table | experiments |
| _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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