Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
J Mol Neurosci. 2013 Jan;49(1):11-20. doi: 10.1007/s12031-012-9836-z. Epub 2012 Jun 16.
Caffeine has been reported to enhance cognition in animal and humans. Additionally, caffeine alleviates cognitive impairment associated with a number of disorders including Alzheimer's disease. The lipophilic nature of caffeine allows for rapid absorption into the bloodstream where it freely crosses the blood-brain barrier. Caffeine promotes dendritic spine growth in cultured hippocampal neurons, which suggests a neuroprotective effect. We examined the effect of chronic caffeine treatment on stress-induced suppression of long-term potentiation (LTP) and impairment of molecules of its signaling cascade. Rats were subjected to daily stress using the psychosocial stress paradigm (intruder model), in vivo recordings from area CA1 of the hippocampus of adult rat, and immunoblot analysis of essential signaling molecules. Caffeine prevented stress-induced LTP impairment. Western blot analysis showed reduction of the basal levels of the phosphorylated calcium calmodulin kinase II (P-CAMKII), total CaMKII, and brain-derived neurotrophic factor (BDNF) in area CA1 of stressed rats. These reductions were prevented by chronic caffeine treatment (0.33 mg/L in drinking water). In addition, caffeine prevented the upregulation of calcineurin levels in stressed rats. High-frequency stimulation (HFS) normally increased P-CaMKII, total CaMKII, and calcineurin levels in control as well as in caffeine-treated stressed rats. However, in stressed rats, the same HFS induced increases in the levels of total CaMKII and calcineurin, but not those of P-CaMKII. The levels of signaling molecules may not reflect activities of these molecules. It appears that the neuroprotective effect of caffeine involves preservation of the levels of essential kinases and phosphatases in stressed rats. This may include preservation of basal levels of BDNF by chronic caffeine treatment in stressed animals. These findings highlight the critical role of P-CaMKII and BDNF in caffeine-induced prevention of stress-induced LTP impairment.
咖啡因已被报道能增强动物和人类的认知能力。此外，咖啡因能减轻包括阿尔茨海默病在内的多种疾病相关的认知障碍。咖啡因的亲脂性使其能迅速被吸收到血液中，并能自由穿过血脑屏障。咖啡因能促进培养的海马神经元中的树突棘生长，这表明它具有神经保护作用。我们研究了慢性咖啡因处理对应激诱导的长时程增强（LTP）抑制和其信号级联分子损伤的影响。大鼠采用心理社会应激范式（入侵者模型）进行每日应激，在体记录成年大鼠海马 CA1 区的电活动，并对关键信号分子进行免疫印迹分析。咖啡因可预防应激诱导的 LTP 损伤。Western blot 分析显示，应激大鼠海马 CA1 区磷酸化钙调蛋白激酶 II（P-CaMKII）、总 CaMKII 和脑源性神经营养因子（BDNF）的基础水平降低。这种降低可被慢性咖啡因处理（饮用水中 0.33mg/L）所预防。此外，咖啡因可预防应激大鼠中钙调神经磷酸酶水平的上调。高频刺激（HFS）通常会增加对照组和咖啡因处理应激大鼠中 P-CaMKII、总 CaMKII 和钙调神经磷酸酶的水平。然而，在应激大鼠中，相同的 HFS 诱导总 CaMKII 和钙调神经磷酸酶水平升高，但 P-CaMKII 水平没有升高。信号分子的水平可能不能反映这些分子的活性。看来，咖啡因的神经保护作用涉及到应激大鼠中关键激酶和磷酸酶水平的维持。这可能包括慢性咖啡因处理在应激动物中对 BDNF 的基础水平的维持。这些发现强调了 P-CaMKII 和 BDNF 在咖啡因诱导的预防应激诱导的 LTP 损伤中的关键作用。
