Enhanced expression of a specific hyperpolarization-activated cyclic @entity377 -gated cation channel (HCN) in surviving dentate gyrus granule cells of @entity1 and experimental XXXX hippocampus.

@entity1 @entity410 @entity131 @entity26038 @entity377 @entity2134 @entity40249 @entity1315 @entity302
Changes in the expression of ion channels, contributing to altered neuronal excitability, are emerging as possible mechanisms in the development of certain @entity1 @entity302 . In previous immature rodent studies of experimental prolonged @entity410 , isoform-specific changes in the expression of hyperpolarization-activated cyclic @entity377 -gated cation channels (HCNs) correlated with long-lasting hippocampal hyperexcitability and enhanced @entity410 susceptibility. Prolonged early-life @entity410 commonly precede @entity1 @entity1315 ( @entity1315 ), suggesting that transcriptional dysregulation of HCNs might contribute to the epileptogenic process. Therefore, we determined whether HCN isoform expression was modified in hippocampi of individuals with @entity1315 . @entity40249 and @entity26038 expression were measured using in situ hybridization and immunocytochemistry in hippocampi from three groups: @entity1315 with @entity131 ( @entity131 ; n = 17), @entity302 hippocampi without @entity131 , or @entity131 ( @entity131 ; n = 10), and autopsy material (n = 10). The results obtained in chronic @entity1 @entity302 were validated by examining hippocampi from the @entity2134 model of chronic @entity1315 . In autopsy and most @entity131 hippocampi, @entity40249 mRNA expression was substantial in pyramidal cell layers and lower in dentate gyrus granule cells (GCs). In contrast, @entity40249 mRNA expression over the GC layer and in individual GCs from @entity302 hippocampus was markedly increased once GC neuronal density was reduced by >50%. @entity40249 mRNA changes were accompanied by enhanced immunoreactivity in the GC dendritic fields and more modest changes in @entity26038 mRNA expression. Furthermore, similar robust and isoform-selective augmentation of @entity40249 mRNA expression was evident also in the @entity2134 animal model of @entity1315 . These findings indicate that the expression of HCN isoforms is dynamically regulated in @entity1 as well as in experimental @entity302 . After experimental @entity410 (i.e., early in the epileptogenic process), the preserved and augmented inhibition onto principal cells may lead to reduced @entity40249 expression. In contrast, in chronic @entity302 hippocampus studied here, the profound loss of interneuronal and principal cell populations and consequent reduced inhibition, coupled with increased dendritic excitation of surviving GCs, might provoke a "compensatory" enhancement of @entity40249 mRNA and protein expression.
