NMDA receptor antagonists MK-801 and memantine induce tolerance to oxygen and glucose deprivation in primary cultures of rat cerebellar granule cells
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Acta Neurobiologiae Experimentalis
ISSN
0065-1400
EISSN
1689-0035
Wydawca
NENCKI INST EXPERIMENTAL BIOLOGY
DOI
URL
Rok publikacji
2014
Numer zeszytu
4
Strony od-do
396-404
Numer tomu
74
Identyfikator DOI
Liczba arkuszy
0,88
Słowa kluczowe
en
calcium transients
glutamate
neuroprotection
OGD
preconditioning
Open access
Tryb otwartego dostępu
Inne
Wersja tekstu w otwartym dostępie
Wersja opublikowana
Licencja otwartego dostępu
Inna
Czas opublikowania w otwartym dostępie
Razem z publikacją
Streszczenia
Język
en
Treść
Preconditioning is an experimental strategy for reducing ischemic brain damage. There are reports that brief exposure of neurons to NMDA-receptor antagonists may be an adequate preconditioning stressor. We studied effects of preconditioning of the cerebellar granule cells (CGC) in primary culture by 30-minute exposure to NMDA receptor antagonists 0.5 mu M MK-801 or 5 mu M memantine. CGC were challenged with oxygen and glucose deprivation (OGD) or excitotoxic glutamate and cell viability was tested 24 h later using calcein/ethidium homodimer-1 staining. We studied glutamate-induced increases in Ca-45 uptake and in the intracellular Ca2+ level assessed with the fluorescent probe fluo-3. The number of living cells in OGD-treated cultures decreased by 42\%. Preconditioning with MK-801 or memantine 24 h earlier reduced. cell death to 8\% and 30\% and 48 h earlier to 27\% and 33\%, respectively. Pretreatment with MK-801 followed by the standard MK-801 wash out was slightly cytoprotective in a glutamate excitotoxicity test performed immediately; the protection increased significantly 24 h after preconditioning. In both cases the extensive wash out of MK-801 after preconditioning resulted in loss of cytoprotection. The increase in the intracellular Ca2+ level evoked by glutamate was decreased 24 h after preconditioning and even halved in the neuronal cultures 48 h after preconditioning with MK-801 and memantine. Glutamate-induced Ca-45 uptake in these cells was decreased by 18\%, irrespective of the time laps after preconditioning. These results demonstrate that preconditioning of CGC with NMDA receptor antagonists induces prolonged tolerance to OGD, which is accompanied by the reduction of glutamate-evoked calcium fluxes. The causal relationship between these effects may be suggested.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
589407