Psychobiology Department, Universidade Federal de São Paulo, Brazil.
Psychobiology Department, Universidade Federal de São Paulo, Brazil.
Neurobiol Learn Mem. 2019 Apr;160:91-97. doi: 10.1016/j.nlm.2018.03.025. Epub 2018 Mar 31.
Sleep deprivation is known to affect memory formation, but how it interacts with different memory systems is not completely understood. Adenosine, a homeostatic regulator of sleep that has an increased extracellular concentration during sleep deprivation, is one of the neuromodulators that may be involved in this interaction. The A adenosine receptor is involved in both sleep regulation and memory formation. Among other pathways, the A receptor decreases cAMP levels in the cytosol and thus also regulates protein kinase A (PKA) and exchange protein activated by cAMP (EPAC) activity. To verify the role of the A receptor in the memory impairment caused by sleep deprivation, we tested the effect of 96 h of sleep deprivation (SD) and the administration of DPCPX, an A receptor antagonist on male Wistar rats prior to the training sessions for two memory tasks that relies on the hippocampal function: the multiple trial inhibitory avoidance (MTIA) task, which also requires the striatum, and the contextual fear conditioning (CFC) task, which does not. We also evaluated the effect of SD, DPCPX and the MTIA training session on the protein expression levels of the A1 receptor, PKA phosphorylation and EPAC activity in both the hippocampus and the striatum. Sleep deprivation impaired the performance in the test sessions of both tasks; DPCPX was able to prevent the impairment in the MTIA test but not in the CFC test. SD increased A receptor protein expression levels in the striatum but not in the hippocampus and also decreased PKA phosphorylation in both structures; DPCPX prevented this decrease in the striatum, but not in the hippocampus. Finally, SD had no effect on EPAC activity in either of the structures. These results indicate that the A adenosine receptors play a role in the memory impairment caused by sleep deprivation in tasks that involve the striatum through modulation of the cAMP/PKA pathway.
睡眠剥夺已知会影响记忆形成，但它与不同记忆系统如何相互作用尚不完全清楚。腺苷是一种调节睡眠的内稳态调节剂，在睡眠剥夺期间其细胞外浓度增加，是可能参与这种相互作用的神经调质之一。A 型腺苷受体参与睡眠调节和记忆形成。在其他途径中，A 受体降低细胞质中的 cAMP 水平，从而也调节蛋白激酶 A（PKA）和 cAMP 激活的交换蛋白（EPAC）的活性。为了验证 A 型受体在睡眠剥夺引起的记忆障碍中的作用，我们测试了 96 小时睡眠剥夺（SD）和 A 型受体拮抗剂 DPCPX 对雄性 Wistar 大鼠的给药作用，然后在两个依赖海马功能的记忆任务的训练课程之前进行：多试抑制回避（MTIA）任务，它还需要纹状体，以及上下文恐惧条件反射（CFC）任务，它不需要。我们还评估了 SD、DPCPX 和 MTIA 训练课程对 A1 受体蛋白表达水平、PKA 磷酸化和海马和纹状体中 EPAC 活性的影响。睡眠剥夺损害了这两个任务测试课程中的表现；DPCPX 能够防止 MTIA 测试中的损害，但不能防止 CFC 测试中的损害。SD 增加了纹状体中的 A 型受体蛋白表达水平，但海马体中没有；SD 还降低了这两种结构中的 PKA 磷酸化；DPCPX 防止了纹状体中的这种降低，但不能防止海马体中的降低。最后，SD 对两种结构中的 EPAC 活性均无影响。这些结果表明，A 型腺苷受体通过调节 cAMP/PKA 途径在涉及纹状体的任务中，在睡眠剥夺引起的记忆障碍中发挥作用。
