title: Decreases in HCN mRNA expression in the hippocampus after kindling and status epilepticus in adult rats.
abstract: OBJECTIVE
  Studies in animal models and patients have implicated changes in hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) expression in the pathogenesis of temporal lobe epilepsy (TLE). However, the nature of HCN changes during the epileptogenic process and their commonality across different TLE models is unknown. Here HCN1 and HCN2 mRNA expression was quantitatively measured at different time points during epileptogenesis in two distinct animal models of TLE; the kainic acid (KA)-induced status epilepticus (SE) and amygdala kindling models.
  
  
  METHODS
  Hippocampal subregions (CA1, CA3, and dentate gyrus [DG]) and entorhinal cortex were dissected at different time-points. For KA-induced SE animals this was 24 h, 7 days (preepileptic), and 6 weeks (epileptic) post status. For amygdala kindling animals this was 2 weeks after reaching either "partially kindled" (one class II/III seizure) or "fully kindled" (five class V seizures) states. Quantification of regional hippocampal neuronal loss in the KA-treated animals was done using NeuN immunofluorescence and confocal microscopy.
  
  
  RESULTS
  HCN mRNA levels decreased in an isoform and region specific manner at all time points after KA-induced SE. The decrease in neuronal number could not account for all reductions in HCN mRNA levels post-KA insult, implicating transcriptional changes. A reduction in HCN2 mRNA levels was also observed in fully kindled animals in the CA3 region.
  
  
  CONCLUSIONS
  A reduction in HCN mRNA levels is present in two different models of TLE. This supports the case that a reduction in HCN channel expression is an accompaniment of epileptogenesis in different adult models of TLE.
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Powell
authors.forename: Caroline
authors.initials: C
authors.lastname: Ng
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: Sheng Hong
authors.initials: SH
authors.lastname: Xu
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foote
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reid
mesh_terms: D000679:Amygdala / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004569:Electroencephalography / Q000379:methods; D004597:Electroshock / Q000009:adverse effects; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D007608:Kainic Acid; D007696:Kindling, Neurologic / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology*; D013997:Time Factors
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578667:Hcn1 protein, rat; C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D012333:RNA, Messenger; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid