CB2R deletion effects on GVHD-induced behavioral changes

Validation Score: 0.900 Price: $0.50 graft versus host disease C57BL/6 mice with B10.BR donor transplants Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting CNR2 in C57BL/6 mice with B10.BR donor transplants. Primary outcome: behavioral changes including immobility and struggling behaviors

Description

This study examined whether genetic deletion of the type 2 cannabinoid receptor (CB2R) could rescue acute behavioral dysregulation produced by graft versus host disease (GVHD) in mice. GVHD was induced by irradiation followed by infusion of bone marrow and splenocytes from major histocompatibility complex-mismatched donors. The researchers compared behavioral outcomes between wild-type mice, global CB2R knockout mice, and mice with CB2R deletion specifically in CX3CR1-expressing cells (including microglia). A comprehensive battery of behavioral tests was performed 14-18 days after transplant to assess various aspects of behavior including locomotor activity, depression-like behavior, social interactions, anhedonia, motor coordination, and anxiety-like behavior.

TARGET GENE
CNR2
MODEL SYSTEM
C57BL/6 mice with B10.BR donor transplants
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
cannabinoid signaling, neuroinflammation
SOURCE
extracted_from_pmid_41958320
PRIMARY OUTCOME
behavioral changes including immobility and struggling behaviors

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%) 0.900 composite

📖 Wiki Pages

CNR2 Gene - Cannabinoid Receptor 2 (CB2)geneCX3CR1-Expressing NeuronscellCX3CR1 Protein (Fractalkine Receptor)proteinCX3CR1 — CX3C Chemokine Receptor 1geneCX3CR1 Modulation TherapytherapeuticCX3CR1 Modulation Therapy for NeurodegenerationideaCX3CR1 PET Imaging — Microglia-Targeted NeuroimagimechanismMicrogliaentityMicrogliacellResearchersindexneuroinflammationmechanismEndocannabinoid System Dysfunction Hypothesis in PhypothesisEndocannabinoid CB2 Receptor Neuronscell

Protocol

GVHD induction by irradiation followed by BM and splenocyte infusion from MHC-mismatched B10.BR donors into C57BL/6 recipients. Behavioral testing battery performed 14-18 days post-transplant including open field, forced swim, social interaction, sucrose consumption, rotarod, and anxiety tests.

Expected Outcomes

Expected that CB2R deletion would protect against GVHD-induced behavioral dysregulation based on previous findings showing protection against neuroinflammation and neuronal loss

Success Criteria

Rescue of GVHD-induced behavioral abnormalities in CB2R knockout mice compared to wild-type mice

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