Structural brain changes in Ser129-phosphorylated alpha-synuclein rats based on voxel-based morphometry
Structural brain changes in Ser129-phosphorylated alpha-synuclein rats based on voxel-based morphometry
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基于体素形态测量的 Ser129 磷酸化 α-突触核蛋白大鼠脑结构变化
DOI：
10.1016/j.bbr.2020.112786
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发表时间：
2020-06
影响因子：
2.7
通讯作者：
Cao Xuebing
中科院分区：
文献类型：
--
作者：
Wang Ji;Tan Yang;Peng Qiwei;Zeng Weiqi;Yang Xiaoman;Chen Chi;Wu Yi;Xu Yan;Cao Xuebing
帕金森病已成为最常见的神经退行性疾病之一。病理变化通常表现为黑质中多巴胺能神经元损失和神经元中异常α-突触核蛋白（α-syn）聚集。α-Syn是路易体的主要成分。然而，缺乏关于异常α-syn聚集的传播的研究，这种聚集导致对大脑结构和功能的特定损害。在本研究中，将全长人α-syn纤维注射到大鼠的内侧前脑束中，实验终点为6个月。通过组织学分析观察异常内源性α-syn聚集和神经纤维质量的病理进展。灰色和白色物质的完整性的变化进行了定量分析，使用基于体素的形态测定法（VBM）。在6个月期间观察到行为变化。组织学分析显示，实验组大鼠纹状体多巴胺转运蛋白水平降低;广泛异常的内源性α-syn积累;实验组神经纤维受损、稀疏和紊乱。VBM显示，术后6个月，与对照组相比，实验组的双侧前缘、双侧下缘、右侧海马和右侧皮质体积减小，而丘脑体积增加。边缘系统和丘脑纤维结构的损伤可能发生在帕金森病的早期阶段。
Parkinson's disease has become one of the most common neurodegenerative diseases. Pathological changes typically manifest following dopaminergic neuron loss in the substantia nigra and abnormal alpha-synuclein (alpha-syn) aggregation in the neurons. alpha-Syn is the major component of Lewy bodies. However, research pertaining to the spread of abnormal alpha-syn aggregations, which results in specific damage to the brain structure and function, is lacking. In the present study, full-length human alpha-syn fibrils were injected into the medial forebrain bundle of rats, with an experimental endpoint of 6 months. Histological analysis was conducted to observe the pathological progress of abnormal endogenous alpha-syn aggregation and nerve fiber quality. Changes in gray and white matter integrity were quantitatively analyzed using voxel-based morphometry (VBM). Behavioral changes were observed over the 6-month period. Histological analysis showed reduced dopamine transporter levels in the striatum of the experimental rats; widespread abnormal endogenous alpha-syn accumulation; and damaged, sparse, and disordered nerve fibers in the experimental group. VBM showed that at 6 months after surgery, bilateral anterior limbic, bilateral inferior limbic, right hippocampal, and right cortical volumes had reduced, whereas thalamic volume had increased in the experimental group compared with that in the control group. Damage to the limbic and thalamic fiber structure may occur in the earlier stages of Parkinson's disease.
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DOI：
10.3233/jpd-179001
发表时间：
2017
期刊：
Journal of Parkinson's disease
影响因子：
--
作者：
Braak H;Del Tredici K
通讯作者：
Del Tredici K
影响因子：
4.7
作者：
Waxman EA;Giasson BI
通讯作者：
Giasson BI
DOI：
10.3174/ajnr.a3178
发表时间：
2013-01
期刊：
AJNR. American journal of neuroradiology
影响因子：
--
作者：
Planetta PJ;Schulze ET;Geary EK;Corcos DM;Goldman JG;Little DM;Vaillancourt DE
通讯作者：
Vaillancourt DE
影响因子：
3.2
作者：
F. V. Bussel;W. Backes;P. Hofman;M. Boxtel;M. Schram;Coen D. A. Stehouwer;J. Wildberger;J. Jansen
通讯作者：
F. V. Bussel;W. Backes;P. Hofman;M. Boxtel;M. Schram;Coen D. A. Stehouwer;J. Wildberger;J. Jansen
影响因子：
16.8
作者：
Zhang Z;Kang SS;Liu X;Ahn EH;Zhang Z;He L;Iuvone PM;Duong DM;Seyfried NT;Benskey MJ;Manfredsson FP;Jin L;Sun YE;Wang JZ;Ye K
通讯作者：
Ye K