Widespread Volumetric Brain Changes following Tooth Loss in Female Mice.

Limor Avivi-Arber,Jason P Lerch,Barry J Sessle,Karen D Davis,Massieh Moayedi,Ze'Ev Seltzer,Miriam Friedel

doi:10.3389/fnana.2016.00121

Abstract

Tooth loss is associated with altered sensory, motor, cognitive and emotional functions. These changes vary highly in the population and are accompanied by structural and functional changes in brain regions mediating these functions. It is unclear to what extent this variability in behavior and function is caused by genetic and/or environmental determinants and which brain regions undergo structural plasticity that mediates these changes. Thus, the overall goal of our research program is to identify genetic variants that control structural and functional plasticity following tooth loss. As a step toward this goal, here our aim was to determine whether structural magnetic resonance imaging (sMRI) is sensitive to detect quantifiable volumetric differences in the brains of mice of different genetic background receiving tooth extraction or sham operation. We used 67 adult female mice of 7 strains, comprising the A/J (A) and C57BL/6J (B) strains and a randomly selected sample of 5 of the 23 AXB-BXA strains (AXB1, AXB4, AXB24, BXA14, BXA24) that were produced from the A and B parental mice by recombinations and inbreeding. This panel of 25 inbred strains of genetically diverse inbred strains of mice is used for mapping chromosomal intervals throughout the genome that harbor candidate genes controlling the phenotypic variance of any trait under study. Under general anesthesia, 39 mice received extraction of 3 right maxillary molar teeth and 28 mice received sham operation. On post-extraction day 21, post-mortem whole-brain high-resolution sMRI was used to quantify the volume of 160 brain regions. Compared to sham operation, tooth extraction was associated with a significantly reduced regional and voxel-wise volumes of cortical brain regions involved in processing somatosensory, motor, cognitive and emotional functions, and increased volumes in subcortical sensorimotor and temporal limbic forebrain regions including the amygdala. Additionally, comparison of the 10 BXA14 and 21 BXA24 mice revealed significant volumetric differences between the two strains in several brain regions. These findings highlight the utility of high-resolution sMRI for studying tooth loss-induced structural brain plasticity in mice, and provide a foundation for further phenotyping structural brain changes following tooth loss in the full AXB-BXA panel to facilitate mapping genes that control brain plasticity following orofacial injury.

Highlights

Loss of teeth remains a significant health problem worldwide
Tooth extraction was associated with significantly decreased volume in many brain regions, including orofacial sensorimotor processing regions such as the S1, M1, and insular cortices, the basal ganglia, paraventricular nucleus of the thalamus and trigeminal motor nucleus
The current study has demonstrated, for the first time, that highresolution Structural magnetic resonance imaging (sMRI) can be used for quantifying small volumetric brain differences between mice of different genetic background and between mice receiving tooth extraction vs. sham operation

Summary

Introduction

Loss of teeth remains a significant health problem worldwide. For example, 20% of senior adults in Western countries are considered “orally disabled,” and tooth loss is associated with a compromised quality of life, manifesting as difficulties in chewing and speaking, pain or alterations in other oral sensations such as stereognosis and proprioception, as well as impaired memory, cognitive and emotional functions (for reviews see Feine and Carlsson, 2003; Crocombe et al, 2009; Avivi-Arber et al, 2011; Trulsson et al, 2012; Sessle et al, 2013; Klineberg et al, 2014; Cerutti-Kopplin et al, 2016). Since life expectancy is progressively increasing in most populations, tooth loss and the associated impairments represent an increasing societal burden (Avivi-Arber et al, 2011; Trulsson et al, 2012) These effects of tooth loss vary substantially across individuals (Haraldson et al, 1988; Zarb et al, 2013; Carr and Brown, 2015), both in terms of the type and severity of the outcomes, and in the rate and quality of recovery. Finding ways to prevent or treat tooth loss-induced impairments depends on knowledge of the involved genetic, cellular, molecular, structural, and functional brain mechanisms, which is currently largely lacking

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