Accumulation of amyloid peptides in the brain plays a key role in the pathogenesis of Alzheimer's disease (AD). Aggregated beta-amyloid (Aβ) peptide increases intracellular reactive oxygen species associated to a deficient antioxidant defense system. Prefrontal cortex plays a key role in memory and learning and is especially susceptible to oxidative stress. The objective of this work was to investigate the effects of an intracerebroventricular (i.c.v.) injection of Aβ (1-42) on 24h patterns of oxidative stress parameters and antioxidant defenses in the rat prefrontal cortex. Four-month-old male Holtzman rats were divided into two groups defined as: control (CO) and Aβ-injected (Aβ). Rats were maintained under12h-light:12h-dark conditions and received water and food ad libitum. Tissues samples were isolated every 6 h during a 24h period. Interestingly, we found that an i.c.v. injection of Aβ(1-42) increased lipid peroxidation, reduced total antioxidant capacity level, phase-shifted the daily peak of reduced glutathione, and had a differential effect on the oscillating catalase and glutathione peroxidase specific activity. Thus, elevated levels of Aβ aggregates-a pathogenic hallmark of AD, caused altered temporal patterns of the cellular redox state in prefrontal cortex rat. These findings might contribute, at least in part, to the understanding of the molecular and biochemical basis of redox changes caused by circadian rhythms alterations observed in AD patients.

大脑中淀粉样肽的积累在阿尔茨海默氏病（AD）的发病机理中起着关键作用。聚集的β-淀粉样蛋白（Aβ）肽会增加与缺乏抗氧化剂防御系统相关的细胞内活性氧。前额叶皮层在记忆和学习中起着关键作用，尤其容易受到氧化应激的影响。这项工作的目的是研究脑室内（icv）注射Aβ（1-42）对大鼠前额叶皮层中24h氧化应激参数和抗氧化防御能力的影响。将四个月大的雄性Holtzman大鼠分为两组，分别为：对照组（CO）和注射Aβ的大鼠（Aβ）。将大鼠保持在12h-光照：12h-黑暗的条件下，并随意饮水和食物。在24小时内每6小时分离一次组织样品。有趣的是，我们发现一次icv注射Aβ（1-42）会增加脂质过氧化作用，降低总抗氧化能力水平，使减少的谷胱甘肽的每日峰相移，并对振荡的过氧化氢酶和谷胱甘肽过氧化物酶的比活性产生不同的影响。因此，升高水平的Aβ聚集体-AD的致病特征-导致额叶前皮质大鼠细胞氧化还原状态的时间模式改变。这些发现可能至少部分有助于理解AD患者中由昼夜节律改变引起的氧化还原变化的分子和生物化学基础。对振荡的过氧化氢酶和谷胱甘肽过氧化物酶的比活性有不同的影响。因此，升高水平的Aβ聚集体-AD的致病特征-导致额叶前皮质大鼠细胞氧化还原状态的时间模式改变。这些发现可能至少部分有助于理解AD患者中由昼夜节律改变引起的氧化还原变化的分子和生物化学基础。对振荡的过氧化氢酶和谷胱甘肽过氧化物酶的比活性有不同的影响。因此，升高水平的Aβ聚集体-AD的致病特征-导致额叶前皮质大鼠细胞氧化还原状态的时间模式改变。这些发现可能至少部分有助于理解AD患者中由昼夜节律改变引起的氧化还原变化的分子和生化基础。