Functional dentate gyrus neurogenesis in a rapid kindling seizure model.
Neurogenesis in the adult mammalian hippocampus resulting in long-term persistence of new neurons with features of capacity for functional activation is recognized. Many stimuli are capable of increasing the rate of neurogenesis, including seizure activity. Whether these insults result in an increased number of new functionally active neurons over and above the baseline rate of neurogenesis is not known. The rapid electrical amygdala kindling (REAK) model of seizures isolates the effects of seizures alone in the absence of neuronal death and the resulting seizures induce expression of c-Fos in the vast majority of dentate gyrus (DG) granule cells. C57BL/6 mice were exposed to REAK then injected with bromodeoxyuridine (BrDU) to label dividing cells, then re-exposed to REAK after a delay period to allow detection of functional activation in new neurons by measurement c-Fos expression in response to seizures. Adult subgranular zone cells migrated into the DG granule cell layer (GCL), assumed a neuronal phenotype and demonstrated seizure-dependent responsiveness. Larger absolute numbers of new neurons demonstrating seizure-dependent activation were found in the GCL of previously kindled mice. Seizures are capable of increasing the number of new neurons with the capacity for functional activation laid down in the postseizure period and incorporated into seizure-activated circuitry.
Smith
Paul D
PD
Centre for Clinical Neurosciences and Neurological Research, St Vincent's Hospital, University of Melbourne, VIC, Australia 3065. paul@neurology.net.au
McLean
Karen J
KJ
Murphy
Michael A
MA
Turnley
Ann M
AM
Cook
Mark J
MJ
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000166:cytology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D007150:Immunohistochemistry; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000166:cytology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos; D001973:Bromodeoxyuridine