Death mechanisms in status epilepticus-generated neurons and effects of additional seizures on their survival.
Status epilepticus (SE) increases neurogenesis in the subgranular zone (SGZ) of the adult dentate gyrus, but many of the newborn cells die, partly through caspase-induced apoptosis. Here we provide immunohistochemical evidence indicating that the caspase-evoked death of the new neurons involves the mitochondrial but not the death-receptor-mediated pathway. Cytochrome c released from mitochondria was found in a subset of progenitor cell progeny, while Fas ligand and tumor necrosis factor 1 receptor-associated domain as well as the mitochondria-related, caspase-independent apoptosis-inducing factor were not detected. We also show that additional seizures, induced at different stages during neuronal differentiation of progenitor cell progeny following SE, neither potentiate cell death mechanisms in the SGZ nor compromise the survival of the new cells. Thus, we found similar expression of cytochrome c, active caspase-3, caspase-cleaved PARP, and TUNEL/Hoechst-positive DNA fragmentation, as well as numbers of new cells in the SGZ in rats exposed to additional seizures at days 6 and 7 or days 33 and 34 following SE as in control animals only subjected to SE. We propose that the degree of survival of newly generated neurons is determined primarily by the initial SE insult and the ensuing pathology in the tissue environment, whereas spontaneous seizures play a minor role.
Ekdahl
Christine T
CT
Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A11, SE-221 84 Lund, Sweden. christine.ekdahl@neurol.lu.se
Zhu
Changlian
C
Bonde
Sara
S
Bahr
Ben A
BA
Blomgren
Klas
K
Lindvall
Olle
O
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D053222:Fas Ligand Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction / Q000502:physiology; D013226:Status Epilepticus / Q000378:metabolism / Q000503:physiopathology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D015703:Antigens, CD; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D045304:Cytochromes c; D020169:Caspases