NMDA receptors and the differential ischemic vulnerability of hippocampal neurons
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NMDA receptors and the differential ischemic vulnerability of hippocampal neurons. / Gee, Christine E; Benquet, Pascal; Raineteau, Olivier; Rietschin, Lotty; Kirbach, Sebastian W; Gerber, Urs.
in: EUR J NEUROSCI, Jahrgang 23, Nr. 10, 01.05.2006, S. 2595-603.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - NMDA receptors and the differential ischemic vulnerability of hippocampal neurons
AU - Gee, Christine E
AU - Benquet, Pascal
AU - Raineteau, Olivier
AU - Rietschin, Lotty
AU - Kirbach, Sebastian W
AU - Gerber, Urs
PY - 2006/5/1
Y1 - 2006/5/1
N2 - Transient cerebral ischemia causes an inhomogeneous pattern of cell death in the brain. We investigated mechanisms, which may underlie the greater susceptibility of hippocampal CA1 vs. CA3 pyramidal cells to ischemic insult. Using an in vitro oxygen-glucose deprivation (OGD) model of ischemia, we found that N-methyl-D-aspartate (NMDA) responses were enhanced in the more susceptible CA1 pyramidal cells and transiently depressed in the resistant CA3 pyramidal cells. The long-lasting potentiation of NMDA responses in CA1 cells was associated with delayed cell death and was prevented by blocking tyrosine kinase-dependent up-regulation of NMDA receptor function. In CA3 cells, the energy deprivation-induced transient depression of NMDA responses was converted to potentiation by blocking protein phosphatase signalling. These results suggest that energy deprivation differentially shifts the intracellular equilibrium between the tyrosine kinase and phosphatase activities that modulate NMDA responses in CA1 and CA3 pyramidal cells. Therapeutic modulation of tyrosine phosphorylation may thus prove beneficial in mitigating ischemia-induced neuronal death in vulnerable brain areas.
AB - Transient cerebral ischemia causes an inhomogeneous pattern of cell death in the brain. We investigated mechanisms, which may underlie the greater susceptibility of hippocampal CA1 vs. CA3 pyramidal cells to ischemic insult. Using an in vitro oxygen-glucose deprivation (OGD) model of ischemia, we found that N-methyl-D-aspartate (NMDA) responses were enhanced in the more susceptible CA1 pyramidal cells and transiently depressed in the resistant CA3 pyramidal cells. The long-lasting potentiation of NMDA responses in CA1 cells was associated with delayed cell death and was prevented by blocking tyrosine kinase-dependent up-regulation of NMDA receptor function. In CA3 cells, the energy deprivation-induced transient depression of NMDA responses was converted to potentiation by blocking protein phosphatase signalling. These results suggest that energy deprivation differentially shifts the intracellular equilibrium between the tyrosine kinase and phosphatase activities that modulate NMDA responses in CA1 and CA3 pyramidal cells. Therapeutic modulation of tyrosine phosphorylation may thus prove beneficial in mitigating ischemia-induced neuronal death in vulnerable brain areas.
KW - Animals
KW - Cell Death
KW - Enzyme Activation
KW - Enzyme Inhibitors
KW - Excitatory Amino Acid Antagonists
KW - Hippocampus
KW - Hypoxia-Ischemia, Brain
KW - Immunohistochemistry
KW - Long-Term Potentiation
KW - Organ Culture Techniques
KW - Patch-Clamp Techniques
KW - Phosphoric Monoester Hydrolases
KW - Protein-Tyrosine Kinases
KW - Pyramidal Cells
KW - Rats
KW - Rats, Wistar
KW - Receptors, N-Methyl-D-Aspartate
U2 - 10.1111/j.1460-9568.2006.04786.x
DO - 10.1111/j.1460-9568.2006.04786.x
M3 - SCORING: Journal article
C2 - 16817862
VL - 23
SP - 2595
EP - 2603
JO - EUR J NEUROSCI
JF - EUR J NEUROSCI
SN - 0953-816X
IS - 10
ER -