Public awareness of traumatic brain injury (TBI) in the military increased recently because of the conflicts in Iraq and Afghanistan where blast injury was the most common mechanism of injury. Besides overt injuries, concerns also exist over the potential adverse consequences of subclinical blast exposures, which are common for many service members. A TBI is a risk factor for the later development of neurodegenerative diseases, including Alzheimer disease (AD)-like disorders. Studies of acute TBI in humans and animals have suggested that increased processing of the amyloid precursor protein (APP) toward the amyloid beta protein (Aβ) may explain the epidemiological associations with AD. In a previous study, however, we found in both rat and mouse models of blast overpressure exposure that rather than increasing, rodent brain Aβ42 levels were decreased after acute blast exposure. Here we subjected APP/presenilin 1 transgenic mice (APP/PS1 Tg) to an extended sequence of repetitive low-level blast exposures (34.5 kPa) administered three times per week over eight weeks. If initiated at 20 weeks of age, these repetitive exposures, which were designed to mimic human subclinical blast exposures, reduced anxiety and improved cognition as well as social interactions in APP/PS1 Tg mice, returning many behavioral parameters in APP/PS1 Tg mice to levels of non-transgenic wild type mice. Repetitive low-level blast exposure was less effective at improving behavioral deficits in APP/PS1 Tg mice when begun at 36 weeks of age. While amyloid plaque loads were unchanged, Aβ 42 levels and Aβ oligomers were reduced in the brain of mice exposed to repetitive low-level blast exposures initiated at 20 weeks of age, although levels did not directly correlate with behavioral parameters in individual animals. These results have implications for understanding the nature of blast effects on the brain and their relationship to human neurodegenerative diseases.

中文翻译：

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重复低水平爆炸暴露改善阿尔茨海默病转基因小鼠模型中的行为缺陷并长期降低 Aβ42

由于伊拉克和阿富汗的冲突，爆炸伤是最常见的伤害机制，因此最近公众对军队中创伤性脑损伤 (TBI) 的认识有所提高。除了明显的伤害，还存在对亚临床爆炸暴露的潜在不良后果的担忧，这对许多服务人员来说很常见。TBI 是神经退行性疾病后期发展的危险因素，包括阿尔茨海默病 (AD) 样疾病。对人类和动物急性 TBI 的研究表明，淀粉样前体蛋白 (APP) 向淀粉样蛋白 (Aβ) 的加工增加可能解释了与 AD 的流行病学关联。然而，在之前的一项研究中，我们发现在爆炸超压暴露的大鼠和小鼠模型中，而不是增加，急性爆炸暴露后，啮齿动物大脑 Aβ42 水平降低。在这里，我们对 APP/presenilin 1 转基因小鼠 (APP/PS1 Tg) 进行延长序列的重复低水平爆炸暴露 (34.5 kPa)，在八周内每周进行三次。如果在 20 周大时开始，这些旨在模拟人类亚临床爆炸暴露的重复暴露，减​​少了焦虑并改善了 APP/PS1 Tg 小鼠的认知以及社交互动，使 APP/PS1 Tg 小鼠的许多行为参数恢复到非转基因野生型小鼠的水平。在 APP/PS1 Tg 小鼠 36 周龄开始时，重复低水平爆炸暴露在改善行为缺陷方面效果较差。虽然淀粉样斑块负荷没有变化，在暴露于 20 周龄开始的重复低水平爆炸暴露的小鼠大脑中，Aβ 42 水平和 Aβ 寡聚体减少，尽管水平与个体动物的行为参数没有直接关联。这些结果对于理解爆炸对大脑的影响的性质及其与人类神经退行性疾病的关系具有重要意义。