Distinct caspase pathways mediate necrosis and apoptosis in subpopulations of hippocampal neurons after status epilepticus.
Status epilepticus in the immature brain induces neuronal injury in the hippocampal formation, but the mode and mechanism of death are poorly understood. Our laboratory has recently investigated the role of caspase-3, -8, and -9 in neuronal injury, using a lithium-pilocarpine model of status epilepticus in 2-week-old rat pups. Our results showed that dying neurons in the dentate gyrus and CA1-subiculum area do not share the same mechanism of death. In CA1-subiculum, caspase-8 upregulation preceded caspase-3 activation in morphologically necrotic neurons. The pan-caspase inhibitor Q-VD-OPH reduced CA1 damage, showing that caspases contribute to status epilepticus-induced necrosis. In the dentate gyrus, dying neurons were caspase-9 and -3 immunoreactive and morphologically apoptotic. It is not clear why the same seizures cause different types of cell death in neurons that are connected in series along the same hippocampal circuit, but the apoptotic dentate neurons express doublecortin, and do not express calbindin-D28k, suggesting that their immaturity may be a factor in producing an apoptotic mode of death.
Lopez-Meraz
Maria-Leonor
ML
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Niquet
Jerome
J
Wasterlain
Claude G
CG
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology; D053181:Caspase 8 / Q000378:metabolism / Q000502:physiology; D053453:Caspase 9 / Q000378:metabolism / Q000502:physiology; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D018891:Dentate Gyrus / Q000473:pathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004789:Enzyme Activation / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D009336:Necrosis; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013226:Status Epilepticus / Q000201:enzymology* / Q000473:pathology
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases