Abstract
Dopamine D2 receptor (D2R) signalling is implicated in limbic seizure propagation and seizure-induced neurodegeneration. D2R-/- mice display increased susceptibility to kainic acid (KA) seizures and seizure-induced apoptosis of hippocampal neurons. Here we further investigated the molecular pathways of KA-induced apoptosis in the D2R-/- hippocampus. Immunoblotting experiments showed a marked induction of caspase 3 in the D2R-/- but not in the wild-type hippocampus, 24 h after the administration of KA. The activation of the Akt/glycogen synthase kinase-3beta (GSK-3beta) pathway that has been implicated in neuronal apoptosis was also studied at the same time. No difference in Akt phosphorylation in the hippocampus was detected between the two genotypes, whereas GSK-3beta phosphorylation was markedly downregulated in D2R-/- mice. Our results suggest that GSK-3beta activation participates, independently of Akt, in the KA-induced apoptosis in the D2R-/- hippocampus.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology
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Disease Models, Animal
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Excitatory Amino Acid Agonists / toxicity
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Glycogen Synthase Kinase 3 / metabolism*
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Glycogen Synthase Kinase 3 / physiology
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Glycogen Synthase Kinase 3 beta
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Hippocampus / drug effects
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Hippocampus / enzymology*
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Hippocampus / metabolism
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Kainic Acid / toxicity
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Mice
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Mice, Knockout
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Nerve Degeneration / chemically induced
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Nerve Degeneration / enzymology*
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Nerve Degeneration / genetics
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Proto-Oncogene Proteins c-akt / physiology
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Receptors, Dopamine D2 / deficiency*
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Receptors, Dopamine D2 / genetics*
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Seizures / chemically induced
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Seizures / enzymology*
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Seizures / genetics
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Signal Transduction / drug effects
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Signal Transduction / physiology
Substances
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Excitatory Amino Acid Agonists
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Receptors, Dopamine D2
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Proto-Oncogene Proteins c-akt
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Glycogen Synthase Kinase 3
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Kainic Acid