Sleep disruption elevates oxidative stress in parvalbumin-positive cells of the rat cerebral cortex
Sleep disruption elevates oxidative stress in parvalbumin-positive cells of the rat cerebral cortex
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DOI：
10.1093/sleep/zsy201
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发表时间：
2019-01-01
期刊：
影响因子：
5.6
通讯作者：
Wisor, Jonathan P.
中科院分区：
文献类型：
--
作者：
Harkness, John H.;Bushana, Priyanka N.;Wisor, Jonathan P.
我们使用了一种新的自动睡眠中断（SD）装置，以确定SD对睡眠的影响和氧化应激的分子标记物在大鼠前额叶皮层（PFC）的小白蛋白（PV）神经元。从Zeitgeber时间（ZT）0至ZT 6，对大鼠进行两次6小时SD，一次采用温和处理方法，另一次采用自动搅拌器，沿着大鼠饲养笼地板的长度运行（一种新的SD方法）。随后对相同的大鼠进行12小时SD，从ZT 0至ZT 12。两种方法都干扰了睡眠，尽管大鼠在温和处理期间比在自动化条件下睡得少。两次SD后，大鼠立即表现出以慢波活动升高为特征的代偿性睡眠。我们测量了前边缘前额叶皮质（前边缘PFC; 6和12小时SD）和眶额叶皮质（12小时SD）中氧化应激标记物8-氧代-2 '-脱氧鸟苷（8-氧代-dG）的强度以及PV和PV细胞相关的神经元周围网标记物紫藤凝集素（WFA）的染色强度。在前边缘PFC中，6小时SD增加了8-oxo-dG、PV和WFA的强度。SD 12小时后，所有神经元中8-oxo-dG的强度升高。PV强度仅在8-oxo-dG或WFA共标记的神经元中升高，而WFA强度没有变化。我们的结论是，在与SD诱导的睡眠驱动，PV神经元在前边缘PFC表现出oxidative stress.Statement of SignificanceSleep deprivation已与显着的健康后果和破坏大脑的正常功能，在人类和动物。在这里，使用一种新的睡眠中断方法，我们发现睡眠中断导致神经元中氧化应激和小清蛋白含量增加。在某些情况下，睡眠中断还导致这些神经元周围的神经元周网增加。这些数据首次显示了睡眠中断与小清蛋白神经元特异性神经化学变化之间的关系。
We used a novel automated sleep disruption (SD) apparatus to determine the impact of SD on sleep and molecular markers of oxidative stress in parvalbumin (PV) neurons in the rat prefrontal cortex (PFC). Rats were subjected to two 6 hr SD sessions from zeitgeber time (ZT) 0 to ZT6, one by the gentle handling method and the other by an automated agitator running the length of the rat's home cage floor (a novel SD method). The same rats were later subjected to a 12 hr SD session from ZT0 to ZT12. Sleep was disrupted with both methods, although rats slept less during gentle handling than during the automated condition. Immediately after both SD sessions, rats displayed compensatory sleep characterized by elevated slow-wave activity. We measured in the prelimbic prefrontal cortex (prelimbic PFC; 6 and 12 hr SD) and orbital frontal cortex (12 hr SD) the intensity of the oxidative stress marker, 8-oxo-2'-deoxyguanosine (8-oxo-dG) as well as the staining intensity of PV and the PV cell-associated perineuronal net marker, Wisteria floribunda agglutinin (WFA). In the prelimbic PFC, 6 hr SD increased the intensity of 8-oxo-dG, PV, and WFA. After 12 hr SD, the intensity of 8-oxo-dG was elevated in all neurons. PV intensity was elevated only in neurons colabeled with 8-oxo-dG or WFA, and no changes were found in WFA intensity. We conclude that in association with SD-induced sleep drive, PV neurons in the prelimbic PFC exhibit oxidative stress.Statement of SignificanceSleep deprivation has been associated with significant health consequences and disruption to the normal function of the brain in humans and animals. Here, using a novel sleep disruption method, we found that sleep disruption led to increased oxidative stress and parvalbumin content in neurons. In some cases, sleep disruption also led to increased perineuronal nets around these neurons. These data are the first to show a relationship between sleep disruption and neurochemical changes specific to parvalbumin neurons.