Laboratory of Studies on the Purinergic System, Federal University of Rio Grande do Sul, Health and Basic Sciences Institute, Department of Biochemistry, Porto Alegre/RS, Brazil.
J Alzheimers Dis. 2013;34(2):509-18. doi: 10.3233/JAD-111982.
Intracerebroventricular (icv) streptozotocin (STZ) administration induces pathological and behavioral alterations similar to those observed in Alzheimer's disease (AD) and is thus considered an experimental model of sporadic AD. Since caffeine (an adenosine receptor antagonist) and selective antagonists of adenosine A2A receptors modify the course of memory impairment in different amyloid-β-based experimental models of AD, we now tested the impact of caffeine on STZ-induced dementia and associated neurodegeneration in the hippocampus as well as on the expression and density of adenosine receptors. Adult male rats received a bilateral infusion of saline or STZ (3 mg/kg, icv), which triggered memory deficits after four weeks, as gauged by impaired object recognition memory. This was accompanied by a reduced NeuN immunoreactivity in the hippocampal CA1 region and an increased expression and density of adenosine A2A receptors (A2AR), but not A1R, in the hippocampus. Caffeine consumption (1 g/L in the drinking water starting 2 weeks before the STZ challenge) prevented the STZ-induced memory impairment and neurodegeneration as well as the upregulation of A2AR. These findings provide the first demonstration that caffeine prevents sporadic dementia and implicate the control of central A2AR as its likely mechanism of action.
侧脑室注射链脲佐菌素（STZ）会引起类似于阿尔茨海默病（AD）的病理和行为改变，因此被认为是散发性 AD 的实验模型。由于咖啡因（一种腺苷受体拮抗剂）和腺苷 A2A 受体的选择性拮抗剂可以改变不同淀粉样蛋白-β为基础的 AD 实验模型中的记忆障碍过程，因此我们现在测试了咖啡因对 STZ 诱导的痴呆和海马体相关神经退行性变以及腺苷受体表达和密度的影响。成年雄性大鼠接受双侧生理盐水或 STZ（3mg/kg，侧脑室注射）输注，四周后会出现记忆缺陷，这可以通过物体识别记忆受损来衡量。这伴随着海马 CA1 区的 NeuN 免疫反应性降低，以及海马体中腺苷 A2A 受体（A2AR）的表达和密度增加（但 A1R 没有增加）。咖啡因摄入（在 STZ 挑战前 2 周开始在饮用水中摄入 1g/L）可预防 STZ 诱导的记忆障碍和神经退行性变，以及 A2AR 的上调。这些发现首次证明咖啡因可预防散发性痴呆，并暗示中枢 A2AR 的控制可能是其作用机制。
