Real-time three-dimensional tracking of single vesicles reveals abnormal motion and pools of synaptic vesicles in neurons of Huntington's disease mice.
Real-time three-dimensional tracking of single vesicles reveals abnormal motion and pools of synaptic vesicles in neurons of Huntington's disease mice.
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DOI：
10.1016/j.isci.2021.103181
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发表时间：
2021-10-22
期刊：
影响因子：
5.8
通讯作者：
Park H
中科院分区：
文献类型：
--
作者：
Chen S;Yoo H;Li CH;Park C;Park G;Tan LY;Jung S;Park H
尽管有缺陷的突触传递被认为在神经退行性疾病中发挥作用，但神经变性期间突触小泡的动力学和囊泡池仍然难以捉摸。在这里，我们对亨廷顿病 (HD) 小鼠模型的皮质神经元中的单个突触小泡进行了实时三维跟踪。与野生型神经元相比，HD 神经元中的囊泡具有更大的净位移和回转半径。在HD神经元中，具有高释放概率（Pr）的囊泡散布在低Pr囊泡中，而在野生型神经元中，高Pr囊泡比低Pr囊泡更接近融合位点。 HD 神经元中的非释放囊泡具有异常高的不规则振荡运动发生率。这些异常的动力学和囊泡池可以通过过度表达 Rab11 来挽救，异常的不规则振荡运动可以通过 jasplakinolide 来挽救。我们的研究揭示了 HD 早期阶段突触小泡的异常动力学和池，提示了神经退行性疾病的可能致病机制。对活体神经元中的单个突触小泡进行实时 3D 跟踪 3D 跟踪显示 HD 神经元中的异常运动和释放小泡池 HD 神经元中的非释放小泡表现出普遍的不规则振荡运动 这些 HD 中的异常可以分别通过 Rab11 和 jasplakinolide 来挽救 生物科学；神经科学；神经科学技术
Although defective synaptic transmission was suggested to play a role in neurodegenerative diseases, the dynamics and vesicle pools of synaptic vesicles during neurodegeneration remain elusive. Here, we performed real-time three-dimensional tracking of single synaptic vesicles in cortical neurons from a mouse model of Huntington's disease (HD). Vesicles in HD neurons had a larger net displacement and radius of gyration compared with wild-type neurons. Vesicles with high release probability (Pr) were interspersed with low-Pr vesicles in HD neurons, whereas high-Pr vesicles were closer to fusion sites than low-Pr in wild-type neurons. Non-releasing vesicles in HD neurons had an abnormally high prevalence of irregular oscillatory motion. These abnormal dynamics and vesicle pools were rescued by overexpressing Rab11, and the abnormal irregular oscillatory motion was rescued by jasplakinolide. Our studies reveal the abnormal dynamics and pools of synaptic vesicles in the early stages of HD, suggesting a possible pathogenic mechanism of neurodegenerative diseases. Real-time 3D tracking of single synaptic vesicles in living neurons was performed 3D tracking revealed abnormal motion and pools of releasing vesicles in HD neurons Non-releasing vesicles in HD neurons showed prevalent irregular oscillatory motion These abnormalities in HD can be rescued by Rab11 and jasplakinolide respectively Biological sciences; Neuroscience; Techniques in neuroscience
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影响因子：
3.7
作者：
Menalled LB;Kudwa AE;Miller S;Fitzpatrick J;Watson-Johnson J;Keating N;Ruiz M;Mushlin R;Alosio W;McConnell K;Connor D;Murphy C;Oakeshott S;Kwan M;Beltran J;Ghavami A;Brunner D;Park LC;Ramboz S;Howland D
通讯作者：
Howland D
DOI：
10.1073/pnas.1809189115
发表时间：
2018-10-23
影响因子：
11.1
作者：
Kokotos AC;Peltier J;Davenport EC;Trost M;Cousin MA
通讯作者：
Cousin MA
影响因子：
5.3
作者：
Li, Xueyi;Standley, Clive;DiFiglia, Marian
通讯作者：
DiFiglia, Marian
影响因子：
13.6
作者：
Li, JY;Plomann, M;Brundin, P
通讯作者：
Brundin, P
影响因子：
6.1
作者：
Marsh J;Alifragis P
通讯作者：
Alifragis P