Caffeine and adenosine A2a receptor antagonists prevent β-amyloid (25-35)-induced cognitive deficits in mice
Caffeine and adenosine A2a receptor antagonists prevent β-amyloid (25-35)-induced cognitive deficits in mice
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DOI：
10.1016/j.expneurol.2006.08.008
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发表时间：
2007-01-01
影响因子：
5.3
通讯作者：
Lara, Diogo R.
中科院分区：
文献类型：
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作者：
Dall'Igna, Oscar P.;Fett, Paulo;Lara, Diogo R.
咖啡因，一种腺苷受体拮抗剂，被发现与阿尔茨海默病的发病率呈负相关。此外，咖啡因保护培养的神经元免受β -淀粉样蛋白诱导的毒性，这一作用被腺苷A（2A）模仿，而不是A(1)受体拮抗剂。我们现在测试了咖啡因政府将是否能预防β -淀粉样蛋白诱导的小鼠认知障碍，以及A（2A）受体阻断是否能模仿这种情况。注射β -淀粉样蛋白25-35片段（A β, 3 nmol）一周后，小鼠在抑制回避和自发交替测试中的表现均受损。长时间单独服用咖啡因（1 mg/ml）没有效果，但在服用A β前30分钟服用急性咖啡因（30 mg/kg）时，可以预防A β诱导的两项任务中的认知障碍。每天注射咖啡因（30mg /kg）或选择性腺苷A（2A）受体拮抗剂SCH58261 （0.5 mg/kg）进行亚慢性（4天）治疗后，观察到同样的保护作用。这提供了第一个直接的体内证据，证明咖啡因和A（2A）受体拮抗剂对A - β诱导的失忆症有保护作用，这促使他们对治疗阿尔茨海默病感兴趣。(c) 2006爱思唯尔公司版权所有。
Consumption of caffeine, an adenosine receptor antagonist, was found to be inversely associated with the incidence of Alzheimer's disease. Moreover, caffeine protects cultured neurons against beta-amyloid-induced toxicity, an effect mimicked by adenosine A(2A) but not A(1) receptor antagonists. We now tested if caffeine administration would prevent beta-amyloid-induced cognitive impairment in mice and if this was mimicked by A(2A) receptor blockade. One week after icv administration of the 25-35 fragment of beta-amyloid (A beta, 3 nmol), mice displayed impaired performance in both inhibitory avoidance and spontaneous alternation tests. Prolonged treatment with caffeine (1 mg/ml) had no effect alone but prevented the A beta-induced cognitive impairment in both tasks when associated with acute caffeine (30 mg/kg) 30 min treatment before A beta administration. The same protective effect was observed after subchronic (4 days) treatment with daily injections of either caffeine (30 mg/kg) or the selective adenosine A(2A) receptor antagonist SCH58261 (0.5 mg/kg). This provides the first direct in vivo evidence that caffeine and A(2A) receptor antagonists afford a protection against A beta-induced amnesia, which prompts their interest for managing Alzheimer's disease. (c) 2006 Elsevier Inc. All rights reserved.