Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia; School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
Neurobiol Aging. 2022 Sep;117:24-32. doi: 10.1016/j.neurobiolaging.2022.03.017. Epub 2022 May 3.
Degeneration of cholinergic neurons in the basal forebrain (BF) contributes to cognitive impairment in Alzheimer's disease (AD) and other disorders. Atrophy of BF volume measured by structural MRI is thought to represent the loss of cholinergic neurons in this structure. As there are multiple types of neurons in the BF as well as glia and axons, whether this MRI measure actually reflects the change of cholinergic neurons has not been verified. In this study, we assessed BF cholinergic neuron number by histological counts and compared with the volume measurements by in vivo MRI in 3xTg mice, a model of familial AD. Both manual and template-based segmentation revealed atrophy of the medial septum (MS), consistent with a significant reduction in cholinergic neuron number. However, MRI-measured volume reduction did not correlate with the reduced cholinergic neuron number. To directly test whether specific loss of cholinergic neurons results in BF atrophy, we selectively ablated the cholinergic neurons in the MS. However, no detectable change in MRI volume was observed between lesioned and unlesioned mice. The results indicate that although loss of cholinergic neurons within the BF likely contributes to volume loss, this volume change cannot be taken as a direct biomarker of cholinergic neuron number.
基底前脑（BF）中的胆碱能神经元退化导致阿尔茨海默病（AD）和其他疾病的认知障碍。结构 MRI 测量的 BF 体积萎缩被认为代表了该结构中胆碱能神经元的丧失。由于 BF 中有多种类型的神经元以及神经胶质和轴突，因此这种 MRI 测量实际上是否反映了胆碱能神经元的变化尚未得到验证。在这项研究中，我们通过组织学计数评估了 BF 胆碱能神经元数量，并将其与 3xTg 小鼠（一种家族性 AD 模型）的体内 MRI 体积测量进行了比较。手动和基于模板的分割都显示出内侧隔核（MS）的萎缩，这与胆碱能神经元数量的显著减少一致。然而，MRI 测量的体积减少与胆碱能神经元数量的减少没有相关性。为了直接测试特定的胆碱能神经元丧失是否导致 BF 萎缩，我们选择性地消融了 MS 中的胆碱能神经元。然而，在受损和未受损的小鼠之间未观察到 MRI 体积的可检测变化。结果表明，尽管 BF 内胆碱能神经元的丧失可能导致体积减少，但这种体积变化不能作为胆碱能神经元数量的直接生物标志物。
