Department of Neurology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Neurosci Lett. 2011 Feb 25;490(2):85-9. doi: 10.1016/j.neulet.2010.12.032. Epub 2010 Dec 22.
Chronic stress can induce cognitive impairment. It is unclear whether a higher susceptibility to chronic stress is associated with the progression of pathological brain aging. Senescence-accelerated prone mouse 8 (SAMP8) is a naturally occurring animal model of accelerated brain aging. Senescence-accelerated resistant mouse 1 (SAMR1) is usually used as the normal control. In this study, we examined the effects of chronic restraint stress (CRS) on learning in the Y-maze, hippocampal cell proliferation, and the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of 4-month-old SAMP8 and SAMR1. The results showed that exposure to CRS impaired learning and hippocampal cell proliferation in SAMP8 and SAMR1 but to a much greater extent in SAMP8. Furthermore, CRS significantly decreased the expression of BDNF protein and mRNA in the hippocampus of SAMP8 and SAMR1. These data indicated that SAMP8 is more sensitive to the deleterious effects of CRS on learning than SAMR1. A greater decrease in hippocampal cell proliferation caused by chronic stress may be part of the underlying mechanism for the more severe learning deficit observed in SAMP8. In addition, our findings suggested a role of BDNF in the stress-induced impairment of learning and hippocampal cell proliferation in both strains.
慢性应激可导致认知障碍。目前尚不清楚对慢性应激的更高易感性是否与病理性脑衰老的进展有关。快速老化品系 8 号小鼠（SAMP8）是一种自然发生的加速脑老化动物模型。快速老化品系 1 号小鼠（SAMR1）通常用作正常对照。在这项研究中，我们研究了慢性束缚应激（CRS）对 4 月龄 SAMP8 和 SAMR1 中 Y 迷宫学习、海马细胞增殖以及脑源性神经营养因子（BDNF）表达的影响。结果表明，CRS 损害了 SAMP8 和 SAMR1 的学习和海马细胞增殖，但在 SAMP8 中更为明显。此外，CRS 显著降低了 SAMP8 和 SAMR1 海马中 BDNF 蛋白和 mRNA 的表达。这些数据表明，SAMP8 对 CRS 对学习的有害影响比 SAMR1 更为敏感。慢性应激引起的海马细胞增殖减少可能是 SAMP8 观察到的更严重学习缺陷的部分潜在机制。此外，我们的研究结果表明 BDNF 在两种品系的应激诱导学习和海马细胞增殖损伤中起作用。
