Sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress in chemogenetic transgenic mouse lines.
Sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress in chemogenetic transgenic mouse lines.
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DOI：
10.1038/s41467-023-38961-0
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发表时间：
2023-05-29
影响因子：
16.6
通讯作者：
Michel, Thomas
中科院分区：
文献类型：
--
作者：
Yadav, Shambhu;Waldeck-Weiermair, Markus;Spyropoulos, Fotios;Bronson, Roderick;Pandey, Arvind K.;Das, Apabrita Ayan;Sisti, Alexander C.;Covington, Taylor A.;Thulabandu, Venkata;Caplan, Shari;Chutkow, William;Steinhorn, Benjamin;Michel, Thomas
氧化应激与心血管和神经退行性疾病有关。在这里，我们报告了在神经元和血管内皮细胞中表达酵母D-氨基酸氧化酶（DAAO）的化学遗传转基因小鼠系的神经血管氧化应激的研究。当这些转基因小鼠被喂食D-氨基酸时，DAAO在靶组织中产生过氧化氢。DAAO-TGCdh 5转基因小鼠在肺内皮特异性Cdh 5启动子的控制下表达DAAO。当我们为这些小鼠提供D-丙氨酸时，它们迅速发展由支配心脏的背根神经节和结状神经节内的神经元中的氧化应激和线粒体功能障碍引起的感觉共济失调。DAAO-TGCdh 5小鼠在慢性化学发生性氧化应激后也发生心脏肥大。这种共济失调、线粒体功能障碍和心脏肥大的组合与弗里德赖希共济失调患者的结果相似。我们的观察表明，神经血管氧化应激足以引起感觉共济失调和心肌肥大。DAAO-TGCdh 5小鼠的研究可以提供Friedreich共济失调的机制见解。氧化应激与心血管和神经退行性疾病有关。在这里，作者展示了转基因化学遗传小鼠品系的研究，这些小鼠发展为神经血管氧化应激引起的感觉性共济失调和心脏肥大。
Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here we report studies of neurovascular oxidative stress in chemogenetic transgenic mouse lines expressing yeast D-amino acid oxidase (DAAO) in neurons and vascular endothelium. When these transgenic mice are fed D-amino acids, DAAO generates hydrogen peroxide in target tissues. DAAO-TGCdh5 transgenic mice express DAAO under control of the putatively endothelial-specific Cdh5 promoter. When we provide these mice with D-alanine, they rapidly develop sensory ataxia caused by oxidative stress and mitochondrial dysfunction in neurons within dorsal root ganglia and nodose ganglia innervating the heart. DAAO-TGCdh5 mice also develop cardiac hypertrophy after chronic chemogenetic oxidative stress. This combination of ataxia, mitochondrial dysfunction, and cardiac hypertrophy is similar to findings in patients with Friedreich’s ataxia. Our observations indicate that neurovascular oxidative stress is sufficient to cause sensory ataxia and cardiac hypertrophy. Studies of DAAO-TGCdh5 mice could provide mechanistic insights into Friedreich’s ataxia. Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here the authors show studies of transgenic chemogenetic mouse lines that develop sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress.
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影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
3.6
作者：
Liguori I;Russo G;Curcio F;Bulli G;Aran L;Della-Morte D;Gargiulo G;Testa G;Cacciatore F;Bonaduce D;Abete P
通讯作者：
Abete P
影响因子：
6
作者：
Cooper, JM;Schapira, AHV
通讯作者：
Schapira, AHV
DOI：
10.1016/j.biocel.2003.12.002
发表时间：
2004-06-01
影响因子：
4
作者：
Chiquet-Ehrismann, R
通讯作者：
Chiquet-Ehrismann, R