Neurotransmitter-stimulated neuron-derived sEVs have opposite effects on amyloid β-induced neuronal damage.
Neurotransmitter-stimulated neuron-derived sEVs have opposite effects on amyloid β-induced neuronal damage.
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神经递质刺激的神经元衍生的 sEV 对淀粉样蛋白诱导的神经元损伤具有相反的作用
DOI：
10.1186/s12951-021-01070-5
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发表时间：
2021-10-15
影响因子：
10.2
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Dou Y;Xie J;Tan Y;Zhang M;Zhao Y;Liu X
兴奋性与抑制性神经递质的比例对于维持神经网络的放电模式至关重要，并且在单个神经元和大脑区域内受到严格调节。兴奋性与抑制性 (E/I) 失衡已被证明参与神经退行性疾病的进展，包括阿尔茨海默病 (AD)。谷氨酸兴奋性毒性和 GABA 能神经元功能障碍似乎是 AD 中神经元细胞死亡的关键组成部分。由于细胞外囊泡（EV）现在被探索为细胞间传递信号的重要载体，我们假设神经元衍生的小囊泡（sEV）的功能可能受到神经递质平衡状态的调节，并且sEV可能影响淀粉样蛋白β（Aβ）对神经元的毒性。本研究旨在揭示不平衡神经递质刺激神经元的 sEV 对 Aβ 诱导的毒性的影响。我们在体内和体外证明了从谷氨酸或 GABA 刺激的神经元中分离的两组 sEV 对 Aβ 毒性的相反作用。 GABA 处理的神经元释放的 sEV 减轻了 Aβ 诱导的损伤，而谷氨酸处理的神经元释放的 sEV 则加剧了 Aβ 的毒性。此外，我们还比较了从谷氨酸/GABA/PBS 处理的神经元中分离的 sEV 的 microRNA (miRNA) 组成。我们的结果表明，谷氨酸和 GABA 相反地调节 sEV 中的 miR-132 水平，导致接受 Aβ 攻击的受体细胞的命运相反。我们的研究结果表明，通过不同的神经递质操纵 sEV 的功能可能会揭示 AD 发病机制，并为 AD 治疗提供有前景的策略。在线版本包含可在 10.1186/s12951-021-01070-5 获取的补充材料。
The ratio of excitatory to inhibitory neurotransmitters is essential for maintaining the firing patterns of neural networks, and is strictly regulated within individual neurons and brain regions. Excitatory to inhibitory (E/I) imbalance has been shown to participate in the progression of neurodegenerative diseases, including Alzheimer's disease (AD). Glutamate excitotoxicity and GABAergic neuron dysfunction appear to be key components of the neuronal cell death that takes place in AD. Since extracellular vesicles (EVs) are now explored as an important vehicle in transmitting signals between cells, we hypothesized that the function of neuron-derived small EVs (sEVs) might be regulated by the status of neurotransmitter balance and that sEVs might affect amyloid β (Aβ) toxicity on neurons. This study aimed to reveal the effects of sEVs from unbalanced neurotransmitter-stimulated neurons on Aβ-induced toxicity. We demonstrated the opposite effects of the two groups of sEVs isolated from neurons stimulated by glutamate or GABA on Aβ toxicity in vivo and in vitro. The sEVs released from GABA-treated neurons alleviated Aβ-induced damage, while those released from glutamate-treated neurons aggravated Aβ toxicity. Furthermore, we compared the microRNA (miRNA) composition of sEVs isolated from glutamate/GABA/PBS-treated neurons. Our results showed that glutamate and GABA oppositely regulated miR-132 levels in sEVs, resulting in the opposite destiny of recipient cells challenged with Aβ. Our results indicated that manipulating the function of sEVs by different neurotransmitters may reveal the mechanisms underlying the pathogenesis of AD and provide a promising strategy for AD treatment. The online version contains supplementary material available at 10.1186/s12951-021-01070-5.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
10.6
作者：
Foss-Feig JH;Adkinson BD;Ji JL;Yang G;Srihari VH;McPartland JC;Krystal JH;Murray JD;Anticevic A
通讯作者：
Anticevic A
DOI：
10.3233/jad-161118
发表时间：
2017
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Kandimalla R;Reddy PH
通讯作者：
Reddy PH
影响因子：
4
作者：
Chivet M;Hemming F;Pernet-Gallay K;Fraboulet S;Sadoul R
通讯作者：
Sadoul R
影响因子：
16
作者：
Chivet M;Javalet C;Laulagnier K;Blot B;Hemming FJ;Sadoul R
通讯作者：
Sadoul R