Vulnerability of postnatal hippocampal neurons to seizures varies regionally with their maturational stage.
The mechanism of status epilepticus-induced neuronal death in the immature brain is not fully understood. In the present study, we examined the contribution of caspases in our lithium-pilocarpine model of status epilepticus in 14 days old rat pups. In CA1, upregulation of caspase-8, but not caspase-9, preceded caspase-3 activation in morphologically necrotic cells. Pretreatment with a pan-caspase inhibitor provided neuroprotection, showing that caspase activation was not an epiphenomenon but contributed to neuronal necrosis. By contrast, upregulation of active caspase-9 and caspase-3, but not caspase-8, was detected in apoptotic dentate gyrus neurons, which were immunoreactive for doublecortin and calbindin-negative, two features of immature neurons. These results suggest that, in cells which are aligned in series as parts of the same excitatory hippocampal circuit, the same seizures induce neuronal death through different mechanisms. The regional level of neuronal maturity may be a determining factor in the execution of a specific death program.
Lopez-Meraz
Maria-Leonor
ML
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Wasterlain
Claude G
CG
Rocha
Luisa L
LL
Allen
Suni
S
Niquet
Jerome
J
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D018692:Antimanic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D064026:Calbindins; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D018692:Antimanic Agents; D051017:Apoptosis Regulatory Proteins; D064026:Calbindins; D061945:Caspase Inhibitors; D003292:Convulsants; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D064030:S100 Calcium Binding Protein G; D010862:Pilocarpine; D008094:Lithium; D020169:Caspases