Morphine and HIV-1 Tat interact to cause region-specific hyperphosphorylation of tau in transgenic mice.
Morphine and HIV-1 Tat interact to cause region-specific hyperphosphorylation of tau in transgenic mice.
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DOI：
10.1016/j.neulet.2020.135502
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发表时间：
2021-01-10
影响因子：
2.5
通讯作者：
Hauser KF
中科院分区：
文献类型：
--
作者：
Ohene-Nyako M;Nass SR;Hahn YK;Knapp PE;Hauser KF
阿片类药物滥用在艾滋病毒感染者中普遍存在，并可能加剧与艾滋病毒相关的年龄相关神经认知障碍。然而，艾滋病毒和阿片类药物在多大程度上共同加速表明大脑衰老的病理特征仍不清楚。在诱导的雄性和雌性hiv - 1tat转基因小鼠纹状体、海马和前额叶皮层中，研究了tau蛋白（pSer396、pSer404、pThr205、pSer202和pThr181）和tau蛋白激酶GSK3β和CDK5/p35的病理磷酸化同型，其中一些小鼠接受了2周递增剂量的吗啡。在雄性小鼠纹状体中，与其他所有组相比，吗啡和Tat共同暴露使pSer396增加。纹状体pSer404和pThr205单独增加，而pSer202和pThr181不变。在Tat转基因雌性和雄性小鼠之间的比较揭示了pThr205的不同结果。未观察到其他与性别相关的tau磷酸化变化。在海马中，Tat增加了pSer396，而其他磷酸化位点不变，pSer202未检测到。在前额叶皮层中，吗啡增加了pSer396水平，而它不受Tat的影响，而其他磷酸化位点则不受影响。tau激酶的评估显示纹状体GSK3β（磷酸化或总）或总CDK5水平没有变化。纹状体磷酸化CDK5和CDK5激活因子p35的水平分别在Tat和吗啡共暴露时升高。P35水平与pSer396水平与Tat和吗啡共暴露正相关。结果揭示了暴露于吗啡、Tat以及独特的吗啡和Tat相互作用诱导的区域特异性tau过度磷酸化。
Opiate abuse is prevalent among HIV-infected individuals and may exacerbate HIV-associated age-related neurocognitive disorders. However, the extent to which HIV and opiates converge to accelerate pathological traits indicative of brain aging remains unknown. The pathological phospho-isotypes of tau (pSer396, pSer404, pThr205, pSer202, and pThr181) and the tau kinases GSK3β and CDK5/p35 were explored in the striatum, hippocampus, and prefrontal cortex of inducible male and female HIV-1 Tat transgenic mice with some receiving escalating doses of morphine for 2 weeks. In the striatum of male mice, pSer396 was increased by co-exposure to morphine and Tat as compared to all other groups. Striatal pSer404 and pThr205 were increased by Tat alone, while pSer202 and pThr181 were unchanged. A comparison between Tat transgenic female and male mice revealed disparate outcomes for pThr205. No other sex-related changes to tau phosphorylation were observed. In the hippocampus, Tat increased pSer396, while other phosphorylation sites were unchanged and pSer202 was not detected. In the prefrontal cortex, morphine increased pSer396 levels, which was unaffected by Tat, while other phosphorylation sites were unaffected. Assessment of tau kinases revealed no changes to striatal GSK3β (phosphorylated or total) or the total CDK5 levels. Striatal levels of phosphorylated CDK5 and p35, the activator of CDK5, were increased by Tat and with morphine co-exposure, respectively. P35 levels positively correlated with those of pSer396 with Tat and morphine co-exposure. The results reveal region-specific hyperphosphorylation of tau induced by exposure to morphine, Tat, and unique morphine and Tat interactions.
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影响因子：
6.1
作者：
Hahn YK;Paris JJ;Lichtman AH;Hauser KF;Sim-Selley LJ;Selley DE;Knapp PE
通讯作者：
Knapp PE
影响因子：
9.9
作者：
Brew, BJ;Pemberton, L;Hagberg, L
通讯作者：
Hagberg, L
影响因子：
64.8
作者：
CACERES, A;KOSIK, KS
通讯作者：
KOSIK, KS
影响因子：
3.6
作者：
Green, AJE;Giovannoni, G;Miller, RF
通讯作者：
Miller, RF
影响因子：
2.5
作者：
GOEDERT, M;JAKES, R;VANMECHELEN, E
通讯作者：
VANMECHELEN, E