Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204-5037, USA.
Mol Cell Neurosci. 2010 Nov;45(3):289-96. doi: 10.1016/j.mcn.2010.06.018. Epub 2010 Jul 15.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cholinergic dysfunction and deposition of beta-amyloid (Aβ) in regions of the brain associated with learning and memory. The sporadic nature and late onset of most AD cases suggests that aside from biological determinants, environmental factors such as stress may also play a role in the progression of the disease. Behavioral and molecular studies were utilized to evaluate the effects of chronic nicotine treatment in the prevention of impairment of long-term memory. The rat model of AD was induced by i.c.v. osmotic pump infusion of Aβ peptides. Chronic psychosocial stress and chronic nicotine treatment were instituted for 6weeks. Spatial memory testing in the Radial Arm Water Maze revealed that, although stress, by itself, did not affect long-term memory, the combination of chronic stress and Aβ infusion impaired long-term memory significantly more than Aβ peptides infusion alone. Chronic nicotine treatment completely prevented Aβ- and stress/Aβ combination-induced memory impairment. Furthermore, molecular findings in hippocampal CA1 region of stress/Aβ rats indicated marked reduction in the protein levels of phosphorylated cAMP response element binding (p-CREB) and calcium-calmodulin-dependent protein kinase IV (CaMKIV), with significant increases in the levels of brain-derived neurotrophic factor (BDNF). These disturbances in signaling pathways, which may be the underlying mechanisms of impairment of long-term memory in these rats, were totally prevented by chronic nicotine treatment.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是胆碱能功能障碍和与学习和记忆相关的大脑区域中β-淀粉样蛋白（Aβ）的沉积。大多数 AD 病例的散发性和发病较晚表明，除了生物学决定因素外，环境因素如压力也可能在疾病的进展中发挥作用。行为和分子研究用于评估慢性尼古丁治疗在预防长期记忆损伤中的作用。AD 的大鼠模型通过 i.c.v. 渗透泵输注 Aβ 肽诱导。进行了 6 周的慢性心理社会压力和慢性尼古丁处理。在放射臂水迷宫中的空间记忆测试表明，尽管压力本身不会影响长期记忆，但慢性应激和 Aβ 输注的组合比单独输注 Aβ 肽更显著地损害长期记忆。慢性尼古丁治疗完全预防了 Aβ 和应激/Aβ 组合诱导的记忆损伤。此外，应激/Aβ 大鼠海马 CA1 区的分子发现表明磷酸化 cAMP 反应元件结合蛋白（p-CREB）和钙调蛋白依赖性蛋白激酶 IV（CaMKIV）的蛋白水平明显降低，而脑源性神经营养因子（BDNF）的水平显著增加。这些信号通路的紊乱可能是这些大鼠长期记忆损伤的潜在机制，而慢性尼古丁治疗完全阻止了这些紊乱。
