Transcriptomic analysis of dorsal and ventral subiculum after induction of acute seizures by electric stimulation of the perforant pathway in rats

Purpose: This study aims to characterize gene expression changes in dorsal and ventral subiculum after the induction of acute seizures by electrical stimulation of the Perforant Pathway (PP) in rats. Methodolody: The dorsal (dSub) and ventral (vSub) subiculum regions were collected by laser- microdissection laser 24 hours after preconditioning protocol, RNA was extracted using Trizol, RNA sequencing was performed in a Hiseq 4000 platform. Reads were aligned to the Rattus norvegicus Ensembl Rnor 5.0 assemble genome using the STAR, DESEq2 statistics package was used to estimate gene expression and for statistical analysis. Results: We identified a total of 1176 differentially expressed genes, in which 204 genes were differentially expressed in dSub and 972 differential expression genes in vSub comparing control to preconditioning samples. The gene ontology enrichment analysis showed that the most significant common enrichment pathway considering up-regulated genes in dSub and vSub was Cholesterol Biosynthesis, while the most significant enrichment pathway considering down-regulated genes in vSub was Axon guidance. Moreover, we found GFAP, C3 and GAD2 up-regulated in dSub and vSub, downregulation of GLS2 in dSub and vSub, and downregulation of GAT-1 in vSub. Conclusion: These findings suggest preconditioning by PP electrical stimulations might induce synaptic reorganization, complement system activation, decreased glutamatergic transmission, and increased GABA transmission in subiculum areas. In the ventral subiculum, the down-regulation of proapoptotic genes and axon guidance indicates that preconditioning induces a neuroprotective environment in this region. Dorsal and Ventral subiculum mRNA profile 24 hours after preconditioning protocol compared to Control dorsal and ventral subiculum mRNA profile