title: Widespread Volumetric Brain Changes following Tooth Loss in Female Mice.
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-mortemwhole-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.
authors.affiliation: University of Toronto Centre for the Study of Pain, University of TorontoToronto, ON, Canada; Faculty of Dentistry, University of TorontoToronto, ON, Canada.
authors.forename: Limor
authors.initials: L
authors.lastname: Avivi-Arber
authors.affiliation: University of Toronto Centre for the Study of Pain, University of TorontoToronto, ON, Canada; Faculty of Dentistry, University of TorontoToronto, ON, Canada; Department of Physiology, Faculty of Medicine, University of TorontoToronto, ON, Canada; Department of Anesthesiology, University Health NetworkToronto, ON, Canada; Central Institute of Mental Health, University of HeidelbergMannheim, Germany.
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Seltzer
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children Toronto, ON, Canada.
authors.forename: Miriam
authors.initials: M
authors.lastname: Friedel
authors.affiliation: Mouse Imaging Centre, Hospital for Sick ChildrenToronto, ON, Canada; Medical Biophysics, Faculty of Medicine, University of TorontoToronto, ON, Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: University of Toronto Centre for the Study of Pain, University of TorontoToronto, ON, Canada; Faculty of Dentistry, University of TorontoToronto, ON, Canada.
authors.forename: Massieh
authors.initials: M
authors.lastname: Moayedi
authors.affiliation: University of Toronto Centre for the Study of Pain, University of TorontoToronto, ON, Canada; Department of Surgery, University of TorontoToronto, ON, Canada; Institute of Medical Science, University of TorontoToronto, ON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, Toronto Western Hospital, University Health NetworkToronto, ON, Canada.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Davis
authors.affiliation: University of Toronto Centre for the Study of Pain, University of TorontoToronto, ON, Canada; Faculty of Dentistry, University of TorontoToronto, ON, Canada; Department of Physiology, Faculty of Medicine, University of TorontoToronto, ON, Canada.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Sessle
keywords: animal model; brain imaging (MRI); genetic variation; neuroplasticity; plasticity; sMRI; tooth loss; trigeminal nerve