Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging.
Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging.
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DOI：
10.1186/s13041-016-0282-7
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发表时间：
2017-01-05
期刊：
影响因子：
3.6
通讯作者：
Awaji T
中科院分区：
文献类型：
--
作者：
Yagishita S;Suzuki S;Yoshikawa K;Iida K;Hirata A;Suzuki M;Takashima A;Maruyama K;Hirasawa A;Awaji T
睡眠呼吸障碍导致认知障碍，并可能与阿尔茨海默病（AD）有关。间歇性低氧治疗（IHT）是一种睡眠呼吸障碍的实验模型，通过未知的机制导致动物认知障碍。在这里，我们将小鼠暴露于IHT方案，并对其海马样品进行生化分析和微阵列分析。特别是，我们进行了基于基因本体（GO）的微阵列分析，以阐明IHT对海马功能的影响，并将其与各种先前报道的实验条件对海马功能的影响进行了比较（参考文献Gene Expression Omnibus，The National Center for Biotechnology Information）。我们的微阵列分析显示，IHT和衰老在一些常见的GO中共享改变，这也在红藻氨酸治疗、Dicer消融或中度谷氨酸过量时观察到。利用京都基因和基因组百科全书PATHWAY数据库对改变的基因进行定位，结果表明，IHT和衰老影响了包括“MAPK信号通路”、“PI 3 K-Akt信号通路”和“神经元突触”在内的多条通路。与基因分析一致，体内分析表明，IHT增加磷酸化tau蛋白，反映了激酶和/或磷酸酶的不平衡，并减少了与突触相关的蛋白质。此外，IHT增加了磷酸化的p70 S6激酶，表明参与了雷帕霉素信号通路的哺乳动物靶点。此外，IHT小鼠在Y-迷宫测试中表现出活动过度，这在AD模型中也观察到。我们从大量的微阵列数据中获得了重要的数据或东西，并通过体内分析证实了IHT诱导的认知障碍的有效性：IHT通过衰老常见的生物学过程增加磷酸化tau蛋白可能部分解释了这一事实。此外，由于衰老是AD的主要危险因素，IHT是研究AD发病病理过程的新模型。本文的在线版本（doi：10.1186/s13041-016-0282-7）包含补充材料，可供授权用户使用。
Sleep-disordered breathing produces cognitive impairments, and is possibly associated with Alzheimer disease (AD). Intermittent hypoxia treatment (IHT), an experimental model for sleep-disordered breathing, results in cognitive impairments in animals via unknown mechanisms. Here, we exposed mice to IHT protocols, and performed biochemical analyses and microarray analyses regarding their hippocampal samples. In particular, we performed gene ontology (GO)-based microarray analysis to elucidate effects of IHT on hippocampal functioning, which were compared with the effects of various previously-reported experimental conditions on that (ref. Gene Expression Omnibus, The National Center for Biotechnology Information). Our microarray analyses revealed that IHT and aging shared alterations in some common GO, which were also observed with kainic acid treatment, Dicer ablation, or moderate glutamate excess. Mapping the altered genes using the Kyoto Encyclopedia of Genes and Genomes PATHWAY database indicated that IHT and aging affected several pathways including “MAPK signaling pathway”, “PI3K-Akt signaling pathway”, and “glutamatergic synapse”. Consistent with the gene analyses, in vivo analyses revealed that IHT increased phosphorylated tau, reflecting an imbalance of kinases and/or phosphatases, and reduced proteins relevant to glutamatergic synapses. In addition, IHT increased phosphorylated p70 S6 kinase, indicating involvement of the mammalian target of rapamycin signaling pathway. Furthermore, IHT mice demonstrated hyperactivity in Y-maze tests, which was also observed in AD models. We obtained important data or something from the massive amount of microarray data, and confirmed the validity by in vivo analyses: the IHT-induced cognitive impairment may be partially explained by the fact that IHT increases phosphorylated tau via biological processes common to aging. Moreover, as aging is a major risk factor for AD, IHT is a novel model for investigating the pathological processes contributing to AD onset. The online version of this article (doi:10.1186/s13041-016-0282-7) contains supplementary material, which is available to authorized users.
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影响因子：
2.4
作者：
Dayyat EA;Zhang SX;Wang Y;Cheng ZJ;Gozal D
通讯作者：
Gozal D
影响因子：
7.8
作者：
Caccamo A;Magrì A;Medina DX;Wisely EV;López-Aranda MF;Silva AJ;Oddo S
通讯作者：
Oddo S
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1523/jneurosci.3367-10.2010
发表时间：
2010-09-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Coleman CG;Wang G;Park L;Anrather J;Delagrammatikas GJ;Chan J;Zhou J;Iadecola C;Pickel VM
通讯作者：
Pickel VM
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J