Induction of neonatal sodium channel II and III alpha-isoform mRNAs in neurons and microglia after status epilepticus in the rat hippocampus.
Sodium channels (NaChs) regulate neuronal excitability in both physiological and pathological conditions, including epilepsy and are therefore an important target for antiepileptic drugs. In the present study, we examined the distribution of mRNAs encoding neonatal NaChs II and III alpha-isoforms in control rat hippocampus and after electrically-induced status epilepticus (SE), using nonradioactive in situ hybridization (ISH). Only weak expression of neonatal NaCh II and III mRNAs was observed in control hippocampus. By contrast, increased expression of neonatal NaCh II and III mRNAs was observed 4 h after the induction of SE in neurons of CA1-CA3 and the dentate granule cell layer. These changes were detected only in rats in which SE was successfully induced and persisted, although less intense, for up to 3 months, when rats display spontaneous seizures. Strong expression of neonatal NaCh alpha-isoforms was observed 1 week after SE in microglial cells, as confirmed by double labelling, combining ISH with immunocytochemistry for microglia markers. The increased expression of neonatal isoforms of the NaCh in both neurons and microglial cells may represent a critical mechanism for modulation of neuronal excitability, glial function and pharmacological response to antiepileptic drugs in the course of epileptogenesis.
Aronica
E
E
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Yankaya
B
B
Troost
D
D
van Vliet
E A
EA
Lopes da Silva
F H
FH
Gorter
J A
JA
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015222:Sodium Channels / Q000235:genetics*; D013226:Status Epilepticus / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution
D020033:Protein Isoforms; D012333:RNA, Messenger; D015222:Sodium Channels