Abstracts

Vagus Nerve Stimulation (VNS) Induces Hippocampal Stem Cell Proliferation in the Rat

Abstract number : 4.083
Submission category : Translational Research-Animal Models
Year : 2006
Submission ID : 6992
Source : www.aesnet.org
Presentation date : 12/1/2006 12:00:00 AM
Published date : Nov 30, 2006, 06:00 AM

Authors :
David Revesz, Mikael Tjernstrom, Thorleif Thorlin, and Elinor Ben-Menachem

The birth of new neurons from neuronal stem cells, the process called neurogenesis, has been seen in adult brains from both rodents and humans. The process is especially prominent in the hippocampus, which is involved in mood and memory functions and epilepsy. A new hypothesis for the development of depression in humans has been formed over the last few years, which includes neurogenesis as a factor of importance in the depressive disease: Reduction of neurogenesis in the hippocampus is a causality factor in the generation of depression and stimulated neurogenesis is part of the recovery process from the depressive state. The same applies for epilepsy. VNS therapy, which has been used successfully for many years in the treatment of epilepsy, was early on in its development noted to have mood elevation effects in VNS treated patients, with effects on depressive symptoms. This anti-depressive effect from VNS has been proven in clinical studies, and VNS is now approved by the FDA for the treatment of severe depression in humans as well as epilepsy. The mechanisms behind the antiepileptic and anti-depressive effects from VNS are, however, not fully understood. We hypothesize that a VNS-induced stimulation of the neurogenesis is part of the mechanism behind the observed clinical effects from VNS., The degree of stem cell proliferation within the dentate gyrus of the hippocampus was studied. The number of new cells were measured by BrdU (bromodeoxy-uridine) incorporation. Immunohistochemistry with antibodies against BrdU were used for the detection of the newly divided cells. Eight rats implanted with VNS-leads and generators were stimulated for two days with the following parameters: 0.75 mA output current, 250 microseconds pulse width, 20 Hz frequency, 30 seconds on and 5 minutes off. These rats were compared with eight control rats that had VNS surgery for implantation of the VNS equipment, but with devices constantly in the off position., There was a statistically significant difference between the two groups with a 50% increase of stem cell proliferation at the 0.03 significance level in the VNS-stimulated rats as compared to sham operated animals., These results indicate that VNS treatment in the rat affects the stem cell proliferation in the hippocampus. In the light of the prevailing theory of a link between hippocampal neurogenesis, epilepsy and depression, this finding might represent an interesting path in the search for mechanisms behind the actions of VNS., (Supported by Cyberonics, Houston, TX, USA; Vastra Gotalandsregionen, Sweden.)
Translational Research