Eva Martin-Solana, Laura Casado-Zueras, Teobaldo E. Torres, Gerardo F. Goya, Maria-Rosario Fernandez-Fernandez, Jose-Jesus Fernandez
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引用次数: 0
Abstract
Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the coding sequence of huntingtin protein. Initially, it predominantly affects medium-sized spiny neurons (MSSNs) of the corpus striatum. No effective treatment is still available, thus urging the identification of potential therapeutic targets. While evidence of mitochondrial structural alterations in HD exists, previous studies mainly employed 2D approaches and were performed outside the strictly native brain context. In this study, we adopted a novel multiscale approach to conduct a comprehensive 3D in situ structural analysis of mitochondrial disturbances in a mouse model of HD. We investigated MSSNs within brain tissue under optimal structural conditions utilizing state-of-the-art 3D imaging technologies, specifically FIB/SEM for the complete imaging of neuronal somas and Electron Tomography for detailed morphological examination, and image processing-based quantitative analysis. Our findings suggest a disruption of the mitochondrial network towards fragmentation in HD. The network of interlaced, slim and long mitochondria observed in healthy conditions transforms into isolated, swollen and short entities, with internal cristae disorganization, cavities and abnormally large matrix granules.
亨廷顿氏病(Huntington's disease,HD)是一种遗传性神经退行性疾病,由亨廷丁蛋白编码序列中一个扩展的 CAG 重复序列引起。最初,它主要影响纹状体的中型棘神经元(MSSN)。目前尚无有效的治疗方法,因此需要寻找潜在的治疗靶点。虽然有证据表明线粒体结构在 HD 中发生了改变,但以往的研究主要采用二维方法,而且是在严格的原生脑环境之外进行的。在本研究中,我们采用了一种新颖的多尺度方法,对 HD 小鼠模型的线粒体紊乱进行了全面的三维原位结构分析。我们利用最先进的三维成像技术,特别是用于神经元体部完整成像的 FIB/SEM 技术和用于详细形态学检查的电子断层扫描技术,以及基于图像处理的定量分析技术,在最佳结构条件下研究了脑组织内的 MSSN。我们的研究结果表明,线粒体网络在 HD 中发生了分裂破坏。在健康状态下观察到的交错、细长的线粒体网络转变为孤立、肿胀和短小的实体,内部嵴紊乱、出现空洞和异常大的基质颗粒。
期刊介绍:
"Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders.
ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.