Avivi-Arber Limor, Seltzer Ze'ev, Friedel Miriam, Lerch Jason P, Moayedi Massieh, Davis Karen D, Sessle Barry J
University of Toronto Centre for the Study of Pain, University of TorontoToronto, ON, Canada; Faculty of Dentistry, University of TorontoToronto, ON, Canada.
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.
Front Neuroanat. 2017 Jan 9;10:121. doi: 10.3389/fnana.2016.00121. eCollection 2016.
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, 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.
牙齿缺失与感觉、运动、认知和情感功能的改变有关。这些变化在人群中差异很大，并伴随着介导这些功能的脑区的结构和功能变化。目前尚不清楚行为和功能的这种变异性在多大程度上是由遗传和/或环境决定因素引起的，以及哪些脑区经历了介导这些变化的结构可塑性。因此，我们研究项目的总体目标是确定控制牙齿缺失后结构和功能可塑性的基因变异。作为朝着这个目标迈出的一步，我们的目的是确定结构磁共振成像（sMRI）是否能够灵敏地检测到接受拔牙或假手术的不同遗传背景小鼠大脑中可量化的体积差异。我们使用了7个品系的67只成年雌性小鼠，包括A/J（A）和C57BL/6J（B）品系，以及从A和B亲本小鼠通过重组和近亲繁殖产生的23个AXB-BXA品系中的5个品系（AXB1、AXB4、AXB24、BXA14、BXA24）的随机样本。这一组25个遗传上不同的近交系小鼠用于绘制整个基因组中包含控制所研究任何性状表型变异的候选基因的染色体区间。在全身麻醉下，39只小鼠接受了右侧上颌三颗磨牙的拔除，28只小鼠接受了假手术。在拔牙后第21天，使用全脑高分辨率sMRI对160个脑区的体积进行量化。与假手术相比，拔牙与参与处理体感、运动、认知和情感功能的皮质脑区的区域和体素水平体积显著减少有关，并且在包括杏仁核在内的皮质下感觉运动和颞叶边缘前脑区体积增加。此外，对10只BXA14小鼠和21只BXA24小鼠的比较显示，两个品系在几个脑区存在显著的体积差异。这些发现突出了高分辨率sMRI在研究小鼠牙齿缺失引起的脑结构可塑性方面的实用性，并为在完整的AXB-BXA组中进一步对牙齿缺失后的脑结构变化进行表型分析提供了基础，以促进绘制控制口腔颌面损伤后脑可塑性的基因。
