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Titolo:
Seizure-induced cell death produced by repeated tetanic stimulation in vitro: Possible role of endoplasmic reticulum calcium stores
Autore:
Pelletier, MR; Wadia, JS; Mills, LR; Carlen, PL;
Indirizzi:
Univ Toronto, Bloorview Epilepsy Res Lab, Toronto, ON M5T 2S8, Canada UnivToronto Toronto ON Canada M5T 2S8 s Lab, Toronto, ON M5T 2S8, Canada Univ Toronto, Playfair Neurosci Unit, Toronto, ON M5T 2S8, Canada Univ Toronto Toronto ON Canada M5T 2S8 Unit, Toronto, ON M5T 2S8, Canada Univ Toronto, Dept Med Neurol, Toronto, ON M5T 2S8, Canada Univ Toronto Toronto ON Canada M5T 2S8 eurol, Toronto, ON M5T 2S8, Canada Univ Toronto, Dept Physiol, Toronto, ON M5T 2S8, Canada Univ Toronto Toronto ON Canada M5T 2S8 ysiol, Toronto, ON M5T 2S8, Canada
Titolo Testata:
JOURNAL OF NEUROPHYSIOLOGY
fascicolo: 6, volume: 81, anno: 1999,
pagine: 3054 - 3064
SICI:
0022-3077(199906)81:6<3054:SCDPBR>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
CA2+ RELEASE CHANNELS; CEREBELLAR GRANULE NEURONS; RAT HIPPOCAMPAL-NEURONS; TEMPORAL-LOBE EPILEPSY; LONG-TERM POTENTIATION; METHYL-D-ASPARTATE; STATUS EPILEPTICUS; RYANODINE RECEPTOR; INOSITOL TRISPHOSPHATE; INTRACELLULAR STORES;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
102
Recensione:
Indirizzi per estratti:
Indirizzo: Pelletier, MR Torontoit,sp, Western Div, Bloorview Epilepsy Res Lab, Playfair Neurosci Un Toronto Hosp MCL 12-413,399 Bathurst St Toronto ON Canada M5T 2S8
Citazione:
M.R. Pelletier et al., "Seizure-induced cell death produced by repeated tetanic stimulation in vitro: Possible role of endoplasmic reticulum calcium stores", J NEUROPHYS, 81(6), 1999, pp. 3054-3064

Abstract

Seizures may cause brain damage due to mechanisms initiated by excessive excitatory synaptic transmission. One such mechanism is the activation of death-promoting intracellular cascades by the influx and the perturbed homeostasis of Ca2+. The neuroprotective effects of preventing the entry of Ca2+ from voltage-dependent Ca2+ channels, NMDA receptors, and non-NMDA receptors, is well known. Less clear is the contribution to excitotoxicity of Ca2+ released from endoplasmic reticulum (ER) stores. We produced epileptiform discharges in combined entorhinal cortex/hippocampus slices using repeated tetanic stimulation of the Schaffer collaterals and assessed cell death after 1, 3, or 12-14 h with gel electrophoresis of genomic DNA and immunohistologically using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine 5'-triphosphate (dUTP) nick end labeling (TUNEL) staining. We manipulated ER Ca2+ stores using two conventional drugs, dantrolene, which blocks the Ca2+ release channel, and thapsigargin, which blocks sarco-endoplasmic reticulum Ca2+-ATPases resulting in depletion of ER Ca2+ stores. To monitorepileptogenesis, and to assess effects attributable to dantrolene and thapsigargin on normal synaptic transmission, extracellular potentials were recorded in stratum pyramidale of the CAI region. Repeated tetanic stimulationreliably produced primary after discharge and spontaneous epileptiform discharges, which persisted for 14 h, the longest time recorded. We did not observe indications of cell death attributable to seizures with either methodwhen assessed after 1 or 3 h; however, qualitatively more degraded DNA always was observed in tetanized slices from the 12- to 14-h group compared with time-matched controls. Consistent with these data was a significant, fourfold, increase in the percentage of TUNEL-positive cells in CA3, CA1, and entorhinal cortex in tetanized slices from the 12- to 14-h group (16.5 +/- 4.4, 33.7 +/- 7.1, 11.6 +/- 2.1, respectively; means +/- SE; n = 7) compared with the appropriate time-matched control (4.1 +/- 2.2, 7.3 +/- 2.0, 2.8 /- 0.9, respectively; n = 6). Dantrolene (30 mu M; n = 5) and thapsigargin(1 mu M: n = 4) did not affect significantly normal synaptic transmission,assessed by the amplitude of the population spike after 30 min of exposure. Dantrolene and thapsigargin also were without effect on the induction or the persistence of epileptiform discharges, but both drugs prevented seizure-induced cell death when assessed with gel electrophoresis. We suggest that Ca2+ entering a cell from the outside, in addition to the Ca2+ contributed from ryanodine-sensitive stores (i.e., Ca2+-induced Ca2+ release), may benecessary for seizure-induced cell death.

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Documento generato il 13/07/20 alle ore 04:54:57