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The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation

Laboratory investigation

Hiroki Toda Division of Neurosurgery, Toronto Western Hospital;
Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan

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 M.D., Ph.D.
,
Clement Hamani Division of Neurosurgery, Toronto Western Hospital;

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 M.D., Ph.D.
,
Adrian P. Fawcett Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada; and

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 Ph.D.
,
William D. Hutchison Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada; and

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 Ph.D.
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Andres M. Lozano Division of Neurosurgery, Toronto Western Hospital;

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 M.D., Ph.D.
Page Range:
132–138
Volume/Issue:
Volume 108: Issue 1
DOI link:
https://doi.org/10.3171/JNS/2008/108/01/0132
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Object

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 μsec, 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.

Abbreviations used in this paper:

AN = anterior nucleus of the thalamus ; BrdU = 5′-bromo-2′-deoxyuridine ; DBS = deep brain stimulation ; DCX = doublecortin ; DG = dentate gyrus of the hippocampus ; GFAP = glial fibrillary acidic protein ; HFS = high frequency stimulation ; NeuN = neuron-specific nuclear protein ; TUNEL = terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling .
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Contributor Notes

Address correspondence to: Andres M. Lozano, M.D., Ph.D., Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst Street WW 4-447, Toronto, Ontario M5T2S8, Canada. email: lozano@uhnres.utoronto.ca.
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