LPS-induced mouse model of depression with synaptic loss analysis

Validation Score: 0.900 Price: $0.50 depression LPS-treated mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting C1q in LPS-treated mice. Primary outcome: depressive and anxiety-like behaviors, synaptic loss, abnormal microglial phagocytosis

Description

This experiment used lipopolysaccharide (LPS) administration to induce a mouse model of depression. Researchers examined the effects of LPS on multiple parameters including depressive and anxiety-like behaviors, synaptic integrity, microglial activation, and microglial phagocytosis of synapses in the hippocampal dentate gyrus. The study focused on understanding how activated microglia dysfunctionally engulf neuronal synapses under depressive conditions, leading to synaptic loss and behavioral impairments. The complement C1q/C3-CR3 signaling pathway was investigated as a potential mediator of this abnormal microglial-synaptic interaction. Behavioral assessments were conducted to evaluate depression and anxiety-like phenotypes, while histological and molecular analyses were performed to assess synaptic density, microglial activation status, and phagocytic activity.

TARGET GENE
C1q
MODEL SYSTEM
LPS-treated mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
C1q/C3-CR3 complement signaling pathway
SOURCE
extracted_from_pmid_38642614
PRIMARY OUTCOME
depressive and anxiety-like behaviors, synaptic loss, abnormal microglial phagocytosis

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

C1QA Gene — Complement Component 1q A ChaingeneC1Q Protein (Complement Component 1q)proteinCR3-Dependent Microglial Synapse Elimination in PamechanismDepression in NeurodegenerationdiseaseDentate GyrusbrainResearchersindexMicrogliacellDepression (Major Depressive Disorder)diseaseMicrogliaentity

Protocol

LPS administration to mice followed by behavioral testing, histological analysis of hippocampal dentate gyrus, assessment of microglial phagocytosis of synapses, and evaluation of C1q/C3-CR3 signaling pathway components

Expected Outcomes

LPS treatment would induce depressive behaviors, activate microglia, increase synaptic phagocytosis, and activate complement signaling

Success Criteria

demonstration of behavioral deficits, synaptic loss, and increased microglial phagocytosis in LPS-treated mice

Related Hypotheses (2)

Astrocyte-Microglia Communication Rebalancing via Cytokine Modulation0.655
TREM2-C1Q Competitive Binding to Prevent Complement-Mediated Cholinergic Synapse Loss0.591

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