Near Infrared Light Treatment Reduces Synaptic Levels of Toxic Tau Oligomers in Two Transgenic Mouse Models of Human Tauopathies.
Near Infrared Light Treatment Reduces Synaptic Levels of Toxic Tau Oligomers in Two Transgenic Mouse Models of Human Tauopathies.
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近红外光处理可降低两种人tauopathies的转基因小鼠模型中有毒tau低聚物的突触水平。
DOI：
10.1007/s12035-018-1248-9
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发表时间：
2019-05
影响因子：
5.1
通讯作者：
Taglialatela G
中科院分区：
文献类型：
--
作者：
Comerota MM;Tumurbaatar B;Krishnan B;Kayed R;Taglialatela G
Tau 寡聚体正在成为突触功能障碍的关键因素，突触功能障碍会导致与阿尔茨海默病 (AD) 的临床表现和进展相关的认知能力下降。因此，人们一致认为，针对 tau 寡聚体的干预措施可能会减缓或阻止 AD 的进展。考虑到这一最终目标，在本研究中，我们在两种转基因小鼠模型中用近红外 (NIR) 光（600-1000 nm）进行体内治疗后，研究了 tau 寡聚体的积累及其突触和行为后果，单独过度表达人类 tau（hTau 小鼠）或与淀粉样蛋白 β（3xTgAD 小鼠）结合。我们发现，暴露于近红外光 4 周（90 秒/天/每周 5 天）可显着降低 hTau 小鼠海马和皮层突触体和总蛋白提取物中内源性总 tau 和寡聚 tau 的水平，并改善恶化的记忆功能。在 3xTgAD 小鼠中也观察到了类似的结果，在近红外光处理后，该小鼠进一步表现出突触 Aβ 减少。另一方面，分离的突触体中 tau 寡聚物的离体结合以及近红外光处理的野生型小鼠海马切片中 tau 寡聚物诱导的长时程增强 (LTP) 抑制不受影响。最后，在近红外光处理的小鼠中，与错误折叠 tau 清除相关的两种机制（诱导型 HSP70 和自噬）关键参与的蛋白质水平上调。总的来说，这些结果表明，近红外光降低了内源性有毒 tau 寡聚体的水平，并减轻了相关的记忆缺陷，从而进一步推动了近红外光作为 AD 可能治疗方法的发展。
Tau oligomers are emerging as a key contributor to the synaptic dysfunction that drives cognitive decline associated with the clinical manifestation and progression of Alzheimer’s disease (AD). Accordingly, there is ample consensus that interventions that target tau oligomers may slow or halt the progression of AD. With this ultimate goal in mind, in the present study, we investigated tau oligomer accumulation and its synaptic and behavioral consequences after an in vivo treatment with near infrared (NIR) light (600–1000 nm) in two transgenic mouse models, overexpressing human tau either alone (hTau mice) or in combination with amyloid beta (3xTgAD mice). We found that a 4-week exposure to NIR light (90 s/day/5 days a week) significantly reduced levels of endogenous total and oligomeric tau in both synaptosomes and total protein extracts from the hippocampus and cortex of hTau mice and improved deteriorating memory function. Similar results were observed in the 3xTgAD mice, which further displayed reduced synaptic Aβ after NIR light treatment. On the other hand, ex vivo binding of tau oligomers in isolated synaptosomes as well as tau oligomer-induced depression of long-term potentiation (LTP) in hippocampal slices from NIR light-treated wt mice were unaffected. Finally, levels of proteins critically involved in two mechanisms associated with clearance of misfolded tau, inducible HSP70 and autophagy, were upregulated in NIR light treated mice. Collectively, these results show that NIR light decreases levels of endogenous toxic tau oligomers and alleviate associated memory deficits, thus furthering the development of NIR light as a possible therapeutic for AD.
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影响因子：
3.3
作者：
Dawson, H. N.;Cantillana, V.;Jansen, M.;Wang, H.;Vitek, M. P.;Wilcock, D. M.;Lynch, J. R.;Laskowitz, D. T.
通讯作者：
Laskowitz, D. T.
影响因子：
4.8
作者：
Jinwal, Umesh K.;Akoury, Elias;Dickey, Chad A.
通讯作者：
Dickey, Chad A.
影响因子：
15.1
作者：
Lasagna-Reeves CA;Castillo-Carranza DL;Sengupta U;Clos AL;Jackson GR;Kayed R
通讯作者：
Kayed R
DOI：
10.1073/pnas.0808084105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Ittner, Lars M.;Fath, Thomas;Goetz, Juergen
通讯作者：
Goetz, Juergen
影响因子：
4
作者：
Castillo-Carranza, Diana L.;Gerson, Julia E.;Kayed, Rakez
通讯作者：
Kayed, Rakez