Purpose: Central nervous system plasticity is essential for normal function, but can also reinforce abnormal network behavior, leading to epilepsy and other disorders. The role of altered ion channel expression in abnormal plasticity has not been thoroughly investigated. Nav1.6 is the most abundantly expressed sodium channel in the nervous system. Because of its distribution in the cell body and axon initial segment, Nav1.6 is crucial for action potential generation. The goal of the present study was to investigate the possible role of changes in Nav1.6 expression in abnormal, activity-dependent plasticity of hippocampal circuits. Methods: We studied kindling, a form of abnormal activity-dependent facilitation. We investigated: (1) sodium channel protein expression by immunocytochemistry and sodium channel messenger RNA (mRNA) by in situ hybridization, (2) sodium current by patch clamp recordings, and (3) rate of kindling by analysis of seizure behavior. The initiation, development, and expression of kindling in wild-type mice were compared to Nav1.6 +/- med tg mice, which have reduced expression of Nav1.6. Results: We found that kindling was associated with increased expression of Nav1.6 protein and mRNA, which occurred selectively in hippocampal CA3 neurons. Hippocampal CA3 neurons also showed increased persistent sodium current in kindled animals compared to sham-kindled controls. Conversely, Nav1.6 +/- medtg mice resisted the initiation and development of kindling. Discussion: These findings suggest an important mechanism for enhanced excitability, in which Nav1.6 may participate in a self-reinforcing cycle of activity-dependent facilitation in the hippocampus. This mechanism could contribute to both normal hippocampal function and to epilepsy and other common nervous system disorders.
DOPAMINERGIC DYSFUNCTION SHOWS A SIMILAR PATTERN IN PATIENTS WITH RING CHROMOSOME 20 EPILEPSY AND TEMPORAL LOBE EPILEPSY / V. Chiesa, A. Del Sole, G. Lucignani, I. Giordano, F. La Briola, A. Vignoli, F. Elisei, L. Gilardi, M. Canevini - In: Epilepsia[s.l] : WILEY-BLACKWELL PUBLISHING, 2009. - pp. 44-45 (( Intervento presentato al 28. convegno International Epilespy Congress tenutosi a Budapest nel 2009.
|Titolo:||DOPAMINERGIC DYSFUNCTION SHOWS A SIMILAR PATTERN IN PATIENTS WITH RING CHROMOSOME 20 EPILEPSY AND TEMPORAL LOBE EPILEPSY|
|Parole Chiave:||Epilepsy; Hippocampus; Kindling; LTP; Persistent sodium current|
|Settore Scientifico Disciplinare:||Settore MED/36 - Diagnostica per Immagini e Radioterapia|
Settore MED/26 - Neurologia
|Data di pubblicazione:||2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1528-1167.2008.01710.x|
|Tipologia:||Book Part (author)|
|Appare nelle tipologie:||03 - Contributo in volume|