The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation.
OBJECTIVE
To examine the influence of deep brain stimulation on hippocampal neurogenesis in an adult rodent model.


METHODS
Rats were anesthetized and treated for 1 hour with electrical stimulation of the anterior nucleus of the thalamus (AN) or sham surgery. The animals were injected with 5'-bromo-2'-deoxyuridine (BrdU) 1-7 days after surgery and killed 24 hours or 28 days later. The authors counted the BrdU-positive cells in the dentate gyrus (DG) of the hippocampus. To investigate the fate of these cells, they also stained sections for doublecortin, NeuN, and GFAP and analyzed the results with confocal microscopy. In a second set of experiments they assessed the number of DG BrdU-positive cells in animals treated with corticosterone (a known suppressor of hippocampal neurogenesis) and sham surgery, corticosterone and AN stimulation, or vehicle and sham surgery.


RESULTS
Animals receiving AN high-frequency stimulation (2.5 V, 90 musec, 130 Hz) had a 2- to 3-fold increase in the number of DG BrdU-positive cells compared with nonstimulated controls. This increase was not seen with stimulation at 10 Hz. Most BrdU-positive cells assumed a neuronal cell fate. As expected, treatment with corticosterone significantly reduced the number of DG BrdU-positive cells. This steroid-induced reduction of neurogenesis was reversed by AN stimulation.


CONCLUSIONS
High-frequency stimulation of the AN increases the hippocampal neurogenesis and restores experimentally suppressed neurogenesis. Interventions that increase hippocampal neurogenesis have been associated with enhanced behavioral performance. In this context, it may be possible to use electrical stimulation to treat conditions associated with impairment of hippocampal function.
Toda
Hiroki
H
Division of Neurosurgery, Toronto Western Hospital, Ontario, Canada.
Hamani
Clement
C
Fawcett
Adrian P
AP
Hutchison
William D
WD
Lozano
Andres M
AM
D000818:Animals; D020643:Anterior Thalamic Nuclei; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D046690:Deep Brain Stimulation; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000502:physiology*
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine