The Effects of Bilateral Vestibular Loss on Hippocampal Volume, Neuronal Number, and Cell Proliferation in Rats

Yiwen Zheng,Ruth Napper,Phoebe Chung,Paul F Smith,Jean Ha Baek,Sangeeta Balabhadrapatruni,Cynthia L Darlington,Catherine Gliddon,Michael Strupp,Ming Zhang,Thomas Brandt

doi:10.3389/fneur.2012.00020

Abstract

Previous studies in humans have shown that bilateral loss of vestibular function is associated with a significant bilateral atrophy of the hippocampus, which correlated with the patients’ spatial memory deficits. More recently, patients who had recovered from unilateral vestibular neuritis have been reported to exhibit a significant atrophy of the left posterior hippocampus. Therefore, we investigated whether bilateral vestibular deafferentation (BVD) would result in a decrease in neuronal number or volume in the rat hippocampus, using stereological methods. At 16 months post-BVD, we found no significant differences in hippocampal neuronal number or volume compared to sham controls, despite the fact that these animals exhibited severe spatial memory deficits. By contrast, using bromodeoxyuridine (BrdU) as a marker of cell proliferation, we found that the number of BrdU-labeled cells significantly increased in the dentate gyrus of the hippocampus between 48 h and 1 week following BVD. Although a substantial proportion of these cells survived for up to 1 month, the survival rate was significantly lower in BVD animals when compared with that in sham animals. These results suggest a dissociation between the effects of BVD on spatial memory and hippocampal structure in rats and humans, which cannot be explained by an injury-induced increase in cell proliferation.

Highlights

There was no significant difference in the total number of neurons between the bilateral vestibular deafferentation (BVD) and sham animals (Figure 2C), no significant interaction between surgery and subregion, but, as expected, a large and significant difference across the five hippocampal subregions [F (4,20) = 141.71, P = 0.000; Figure 2C]
Analysis of the volume data showed that there was no significant difference between the BVD and sham animals, no significant interaction between surgery and subregion, but a large and significant difference in volume across the five hippocampal subregions [F (4,20) = 20.83, P = 0.000; Figure 2D]
The results of this study show that, unlike humans with BVD, who exhibit a significant bilateral atrophy of the hippocampus (Brandt et al, 2005) and with unilateral vestibular neuritis who exhibit a significant atrophy of the left posterior hippocampus www.frontiersin.org

Summary

Introduction

Many studies in animals and humans have shown that loss of vestibular function, especially complete bilateral vestibular loss, can impair spatial memory (e.g., Stackman and Herbert, 2002; Wallace et al, 2002; Russell et al, 2003a; Brandt et al, 2005; Zheng et al, 2006, 2007, 2009a,b; Smith et al, 2009, 2010; Baek et al, 2010; Besnard et al, 2012). London taxi drivers were reported to have increased hippocampal volume compared to controls (Maguire et al, 2000) Consistent with this finding, Hüfner et al (2010) reported structural changes in the hippocampi of professional dancers and slackliners (who traverse a tightrope which is not held completely taut), who have unusual spatial memory experience, including specific vestibular stimulation. Hüfner et al found that trained subjects exhibited a smaller anterior volume, and a larger posterior volume, in the hippocampal formation, they showed no difference in spatial memory compared to controls, according to the virtual Morris water maze test. These studies suggest that spatial memory experience may regulate the volume of different regions of the human hippocampus. In rats, Besnard et al (2012) found no significant difference in hippocampal volume following bilateral intratympanic injections of sodium arsanilate

Methods

Results

Conclusion