کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8686334 | 1580603 | 2018 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Neuronal levels and sequence of tau modulate the power of brain rhythms
ترجمه فارسی عنوان
سطوح و توالی مغز و اعصاب موجب تقویت قدرت ریتم مغز می شود
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
چکیده انگلیسی
Neural network dysfunction may contribute to functional decline and disease progression in neurodegenerative disorders. Diverse lines of evidence suggest that neuronal accumulation of tau promotes network dysfunction and cognitive decline. The A152T-variant of human tau (hTau-A152T) increases the risk of Alzheimer's disease (AD) and several other tauopathies. When overexpressed in neurons of transgenic mice, it causes age-dependent neuronal loss and cognitive decline, as well as non-convulsive epileptic activity, which is also seen in patients with AD. Using intracranial EEG recordings with electrodes implanted over the parietal cortex, we demonstrate that hTau-A152T increases the power of brain oscillations in the 0.5-6â¯Hz range more than wildtype human tau in transgenic lines with comparable levels of human tau protein in brain, and that genetic ablation of endogenous tau in Maptâ/â mice decreases the power of these oscillations as compared to wildtype controls. Suppression of hTau-A152T production in doxycycline-regulatable transgenic mice reversed their abnormal network activity. Treatment of hTau-A152T mice with the antiepileptic drug levetiracetam also rapidly and persistently reversed their brain dysrhythmia and network hypersynchrony. These findings suggest that both the level and the sequence of tau modulate the power of specific brain oscillations. The potential of EEG spectral changes as a biomarker deserves to be explored in clinical trials of tau-lowering therapeutics. Our results also suggest that levetiracetam treatment is able to counteract tau-dependent neural network dysfunction. Tau reduction and levetiracetam treatment may be of benefit in AD and other conditions associated with brain dysrhythmias and network hypersynchrony.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 117, September 2018, Pages 181-188
Journal: Neurobiology of Disease - Volume 117, September 2018, Pages 181-188
نویسندگان
Melanie Das, Sumihiro Maeda, Bozhong Hu, Gui-Qiu Yu, Weikun Guo, Isabel Lopez, Xinxing Yu, Chao Tai, Xin Wang, Lennart Mucke,