Scavenger Receptor Class B Type I Modulates Epileptic Seizures and Receptor α2δ-1 Expression

Abstract

Scavenger receptor class B type I (SR-BI) is abundant in adult mouse and human brains, but its function in the central nervous system (CNS) remains unclear. This study explored the role of SR-BI in epilepsy and its possible underlying mechanism. Expression patterns of SR-BI in the brains of mice with kainic acid (KA)-induced epilepsy were detected using immunofluorescence staining, quantitative real-time polymerase chain reaction (qPCR), and Western blotting(WB). Behavioral analysis was performed by 24-hour video monitoring and hippocampal local field potential (LFP) recordings were employed to verify the role of SR-BI in epileptogenesis. RNA sequencing (RNA-seq) was used to obtain biological information on SR-BI in the CNS. WB, qPCR, and co-immunoprecipitation (Co-IP) were performed to identify the relationship between SR-BI and the gabapentin receptor α2δ-1.The results showed that SR-BI was primarily co-localized with astrocytes and its expression was down-regulated in the hippocampus of KA mice. Notably, overexpressing SR-BI alleviated the epileptic behavioral phenotype in KA mice. Hippocampal transcriptomic analysis revealed 1043 differentially expressed genes (DEGs) in the SR-BI-overexpressing group. Most DEGs confirmed by RNA-seq analysis were associated with synapses, neuronal projections, neuron development, and ion binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the DEGs were enriched in the glutamatergic synapse pathway. Furthermore, the gabapentin receptor α2δ-1 decreased with SR-BI overexpression in epileptic mice. Overall, these findings highlight the important role of SR-BI in regulating epileptogenesis and that the gabapentin receptor α2δ-1 is a potential downstream target of SR-BI.