Rab27a knockdown effects on microglia activation in developing brain

Validation Score: 0.800 Price: $0.50 Neonatal mice with dorsal subventricular zone manipulation Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting Rab27a in Neonatal mice with dorsal subventricular zone manipulation. Primary outcome: Changes in microglia morphology and number following Rab27a knockdown

Description

Neonatal electroporation and shRNA-mediated knockdown of Rab27a was performed in dorsal subventricular zone neural stem cells (NSCs) and astrocytes. This manipulation increased the number of CD11b/IBA1 positive rounded microglia, suggesting that disruption of EV release machinery affects microglial activation state. The experiment demonstrated that EV release pathways, particularly those involving Rab27a, are important for regulating microglial morphology and potentially activation in the developing nervous system.

TARGET GENE
Rab27a
MODEL SYSTEM
Neonatal mice with dorsal subventricular zone manipulation
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
EV release machinery and microglia activation
SOURCE
extracted_from_pmid_30816224
PRIMARY OUTCOME
Changes in microglia morphology and number following Rab27a knockdown

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.800 composite

📖 Wiki Pages

RAB27A GenegeneRAB27A Protein (Ras-Related Protein Rab-27A)proteinIBA1 ProteinproteinAstrocytescellMicrogliacellSubventricular Zone Neural Stem CellscellAstrocytesentityMicrogliaentityEli Lilly Blood-Brain Barrier Delivery PlatformtherapeuticAstrocytes in Argyrophilic Grain DiseasecellAstrocytes in Amyotrophic Lateral SclerosiscellSection 244: Advanced Bioenergetics and ATP RestortherapeuticAstrocytes in Hepatic EncephalopathycellMitochondria-Lysosome Contact Site Dysfunction in hypothesisExosome Biogenesis in Neurodegenerationmechanism

Protocol

Neonatal electroporation, shRNA-mediated knockdown, immunofluorescence analysis of microglia

Expected Outcomes

Increased rounded microglia following disruption of EV release

Success Criteria

Significant increase in CD11b/IBA1 positive rounded microglia

Related Hypotheses (1)

RAB27A-dependent extracellular vesicle engineering for mitochondrial cargo delivery0.674

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