Seizures, not hippocampal neuronal death, provoke neurogenesis in a mouse rapid electrical amygdala kindling model of seizures.
OBJECTIVE
Proliferation of neural precursors adjacent to the granule cell layer of the dentate gyrus has been identified in previous epilepsy models. Convincingly demonstrating that seizure activity is the stimulant for neurogenesis, rather than neuronal death or other insults inherent to seizure models, is difficult. To address this we derived a rapid electrical amygdala kindling model in mice known to be resistant to seizure-induced neuronal death as an experimental model of focal seizures and to analyze subsequent neurogenesis.


METHODS
Mice were implanted with bipolar electrodes in the left amygdala and given electrical stimulation (3 s, 100 Hz, 1 ms monophasic square wave pulses every 5 min, 40 in total) while being observed and graded for the development of seizures. Neurogenesis in the hippocampus was assessed by counting bromodeoxyuridine-immunoreactive cells co-labeled for astrocyte (glial fibrillary acidic protein) and neuronal nuclear markers.


RESULTS
Bromodeoxyuridine-reactive cell numbers were three-fold higher in stimulated mice compared with controls at 1 week in the subgranular region and at three weeks extensive co-labeling with neuronal nuclear was noted in cells which had migrated into the body of the granule cell layer, while mice receiving stimulation but failing to kindle did not differ significantly from controls. No increase in neuronal death was detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, Fluorojade or fluorescent examination of hematoxylin and eosin-stained sections in any inter-group comparison.


CONCLUSIONS
We propose that this kindling paradigm, not previously applied to mice, demonstrates more convincingly than previously the surge in neurogenesis in response to seizures, and the effects of seizures alone in regard to neuronal injury and regeneration.
Smith
P D
PD
Centre for Clinical Neurosciences and Neurological Research, St. Vincent's Hospital, Melbourne, Victoria, Australia. paul@neurology.net.au
McLean
K J
KJ
Murphy
M A
MA
Turnley
A M
AM
Cook
M J
MJ
D000818:Animals; D000963:Antimetabolites; D001522:Behavior, Animal / Q000502:physiology; D001973:Bromodeoxyuridine; D016923:Cell Death; D049109:Cell Proliferation; D003594:Cytoplasmic Granules / Q000502:physiology; D018891:Dentate Gyrus / Q000473:pathology; D004569:Electroencephalography; D005838:Genotype; D006624:Hippocampus / Q000254:growth & development* / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007696:Kindling, Neurologic / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000502:physiology; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D012640:Seizures / Q000473:pathology*
D000963:Antimetabolites; D001973:Bromodeoxyuridine