Gestational haloperidol exposure effects on hippocampal gene expression

Validation Score: 0.900 Price: $0.50 schizophrenia pregnant mice and offspring Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting Nr3c1 in pregnant mice and offspring. Primary outcome: differential gene expression in hippocampus

Description

This study investigated the molecular biological changes in fetal hippocampus following prenatal exposure to haloperidol (HAL) as a model of schizophrenia-like developmental disruption. Pregnant mice were administered haloperidol (1 mg/kg/day) during gestation, and the hippocampal tissue from offspring was analyzed using RNA-sequencing to identify differentially expressed genes. The study aimed to understand how prenatal antipsychotic exposure, an environmental risk factor, induces apoptotic neurodegeneration and cognitive impairment similar to schizophrenia. RNA-sequencing revealed significant gene expression changes, with particular focus on Nr3c1 mRNA upregulation. The research also included in silico analysis to predict microRNA regulation of the observed gene expression changes, specifically investigating miR-137-3p as a potential regulator of Nr3c1 expression.

TARGET GENE
Nr3c1
MODEL SYSTEM
pregnant mice and offspring
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
glucocorticoid signaling, microRNA regulation
SOURCE
extracted_from_pmid_35859315
PRIMARY OUTCOME
differential gene expression in hippocampus

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

RNA Metabolism Dysregulation PathwaymechanismRNA Processing in NeurodegenerationmechanismRNA Metabolism Dysregulation in 4R-TauopathiesmechanismRNA Metabolism in Alzheimer's DiseasemechanismRNA Metabolism in NeurodegenerationmechanismRNA Binding Fox-3 Homolog (NeuN) (RBFOX3)geneRNA Therapeutics: Investment Landscape AnalysisinvestmentRNA Therapeutics for Neurodegeneration Investment investmentRNA Metabolism Dysfunction in Corticobasal SyndrommechanismRNA Binding Fox-1 Homolog 1 (RBFOX1)geneRNA Binding Fox-1 Homolog 2 (RBFOX2)geneRNA Granule Dysfunction in NeurodegenerationmechanismRNA Metabolism Dysregulation in Alzheimer's DiseasmechanismRNA G-quadruplexes in NeurodegenerationmechanismRNA Splicing in Neurodegenerationmechanism

Protocol

Pregnant mice administered HAL (1 mg/kg/day), offspring hippocampus harvested for RNA-sequencing analysis, qPCR validation of selected genes, in silico prediction of miRNA regulation

Expected Outcomes

Altered gene expression patterns in hippocampus of HAL-exposed offspring, particularly changes in Nr3c1 expression and miR-137-3p regulation

Success Criteria

Significant differential gene expression (P < 0.05 and q < 0.05), successful qPCR validation of RNA-seq findings

Related Hypotheses (1)

Multi-Modal Stress Response Harmonization0.756

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