Induction of neurogenesis in the adult dentate gyrus by cortical spreading depression.
OBJECTIVE
Spreading depression (SD) is an epiphenomenon of neurological disorders, like stroke or traumatic brain injury. These diseases have been associated with an increased neurogenesis in the adult rodent dentate gyrus. Such proliferative activity can also be induced by conditions that--like SD--coincide with a disturbed neuronal excitability, eg, epilepsy. Thus we hypothesized that SD might likewise influence hippocampal neurogenesis and potentially act as mediator of injury-induced neurogenesis.


METHODS
Repetitive cortical SD were induced by epidural application of 3 mol/L KCl. At different time points thereafter dentate gyrus neurogenesis was investigated by means of intraperitoneal bromodeoxyuridine injections and immunocytochemistry. Spatial learning and memory was tested in a Morris water maze.


RESULTS
Cortical SD significantly increased proliferative activity in the ipsilateral subgranular zone on days 2 and 4. We detected about 280% more newborn cells in the dentate gyrus of rats that received bromodeoxyuridine during the first week after SD and were allowed to recover for 6 weeks. Most of these cells expressed the mature neuronal marker NeuN. The mitogenic action of SD was suppressed by systemic administration of the NMDA receptor antagonist MK-801. Behavioral performance of SD animals in the Morris water maze did not improve significantly.


CONCLUSIONS
From our data we postulate that the increased dentate gyrus neurogenesis observed after brain injury may at least partly be mediated by SD-like epiphenomena. Furthermore they indicate that even a strongly enhanced dentate gyrus neurogenesis may occur without significant improvements in hippocampus-dependent spatial learning and memory.
Urbach
Anja
A
Department of Neurology, Friedrich-Schiller-University, Jena, Germany. anja.urbach@med.uni-jena.de
Redecker
Christoph
C
Witte
Otto W
OW
D000818:Animals; D000963:Antimetabolites / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D013181:Cortical Spreading Depression / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011597:Psychomotor Performance; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000502:physiology
D000963:Antimetabolites; D015415:Biomarkers; D001973:Bromodeoxyuridine