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Titolo:
Changes in the mRNAs encoding voltage-gated sodium channel types II and III in human epileptic hippocampus
Autore:
Whitaker, WRJ; Faull, RLM; Dragunow, M; Mee, EW; Emson, PC; Clare, JJ;
Indirizzi:
Babraham Inst, Dept Neurobiol, Cambridge CB2 4AT, England Babraham Inst Cambridge England CB2 4AT biol, Cambridge CB2 4AT, England Univ Auckland, Dept Anat, Auckland, New Zealand Univ Auckland Auckland New Zealand nd, Dept Anat, Auckland, New Zealand Univ Auckland, Dept Pharmacol, Auckland, New Zealand Univ Auckland Auckland New Zealand ept Pharmacol, Auckland, New Zealand Auckland Hosp, Dept Neurosurg, Auckland, New Zealand Auckland Hosp Auckland New Zealand ept Neurosurg, Auckland, New Zealand GlaxoWellcome Med Res Ctr, Dept Mol Pharmacol, Stevenage SG1 2NY, Herts, England GlaxoWellcome Med Res Ctr Stevenage Herts England SG1 2NY Herts, England
Titolo Testata:
NEUROSCIENCE
fascicolo: 2, volume: 106, anno: 2001,
pagine: 275 - 285
SICI:
0306-4522(2001)106:2<275:CITMEV>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
KAINATE-INDUCED SEIZURES; DIFFERENTIAL UP-REGULATION; SUBUNIT MESSENGER-RNAS; DEPENDENT NA+ CHANNELS; CENTRAL-NERVOUS-SYSTEM; RAT MUSCLE-CELLS; ALPHA-SUBUNIT; ELECTRICAL-ACTIVITY; DOWN-REGULATION; GROWTH-FACTOR;
Keywords:
sodium channels; human brain; mRNA distribution; epilepsy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Clare, JJ Babraham Inst, Dept Neurobiol, Cambridge CB2 4AT, England Babraham Inst Cambridge England CB2 4AT ridge CB2 4AT, England
Citazione:
W.R.J. Whitaker et al., "Changes in the mRNAs encoding voltage-gated sodium channel types II and III in human epileptic hippocampus", NEUROSCIENC, 106(2), 2001, pp. 275-285

Abstract

Studies with animal seizure models have indicated that changes in temporaland spatial expression of voltage-gated sodium channels may be important in the pathology of epilepsy. Here, by using in situ hybridisation with previously characterised subtype-selective oligonucleotide probes [Whitaker et al. (2000) J. Comp. Neurol. 422, 123-139], we have compared the cellular expression of all four brain alpha -subunit sodium channel mRNAs in 'normal' and epileptic hippocampi from humans. Neuronal cell loss was observed in all regions of the hippocampus of diseased patients, indicating that sclerosis had occurred. Losses of up to 40% compared to post-mortem controls were observed which were statistically significant in all regions studied (dentate gyrus, hilus, and CA1-3). To assess mRNA levels of the different a-subtypes in specific subregions, control and diseased tissue sections were hybridised to subtype-specific probes. To quantify any changes in expression while allowing for cell loss, the sections were processed for liquid emulsion autoradiography and grain counts were performed on populations of individual neurones in different subregions. No significant differences were found in the expression of type I and VI mRNAs. In contrast, a significant down-regulation of type II mRNA wasobserved in the epileptic tissue in the remaining pyramidal cells of CA3 (71 +/- 7% of control, P < 0.01), CA2 (81 +/- 8% of control, P < 0.05) and CA1 (72 +/- 6% of control, P < 0.05) compared with control tissue. Additionally, a significant up-regulation in type III mRNA in epileptic CA4 pyramidal cells (145 +/- 7% of control, P < 0.05) was observed. It is not clear whether these changes play a causal role in human epilepsyor whether they are secondary to seizures or drug treatment; further studies are necessary to investigate these alternatives. However, it is likely that such changes would affect the intrinsic excitability of hippocampal neurones. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.

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Documento generato il 29/03/20 alle ore 17:06:27