Differential regulation of hippocampal transcriptome by circulating estrogen

Area of Science:

• Neuroscience
• Molecular Biology
• Endocrinology

Background:

• Estrogen (E2) significantly influences hippocampal synaptic structure and plasticity.
• Fluctuations in E2 during the menstrual cycle are linked to changes in women's cognition, emotion, and behavior.
• Understanding E2's molecular effects in the hippocampus is crucial for deciphering its role in neurological functions and disorders.

Purpose of the Study:

• To investigate the impact of E2 levels during proestrus (PE) and diestrus (DE) stages on hippocampal gene expression in female rats.
• To identify differentially expressed genes (DEGs) in the hippocampus between PE and DE stages using RNA-sequencing.
• To elucidate the functional pathways affected by E2-mediated gene expression changes in the hippocampus.

Main Methods:

• RNA-sequencing (RNA-seq) was performed on hippocampal tissues from young female rats at the PE and DE stages of the estrus cycle.
• Differential gene expression analysis was conducted using a 1.5-fold-change threshold and an FDR-adjusted p-value < 0.05.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were employed to interpret the functional significance of DEGs.
• Quantitative real-time PCR (qPCR) was used to validate the expression levels of selected DEGs.

Main Results:

• A total of 238 DEGs were identified between the PE and DE stages, responsive to E2 fluctuations.
• Functional analysis indicated that higher E2 levels (PE stage) correlated with increased gene transcription for most DEGs.
• KEGG analysis revealed upregulation of genes involved in neuroactive ligand-receptor interaction and cell adhesion in the PE stage, while DEGs related to bile secretion and coagulation cascades were upregulated in the DE stage.

Conclusions:

• This study provides a comprehensive transcriptomic profile of the hippocampus in response to E2 variations across the estrus cycle in female rats.
• The identified DEGs and associated pathways offer fundamental insights into the neuro-molecular mechanisms underlying E2's influence on hippocampal function.
• These findings lay the groundwork for further research into the relationship between E2 fluctuations, hippocampal plasticity, and associated cognitive and emotional disorders.