Zhao W Q, Polya G M, Wang B H, Gibbs M E, Sedman G L, Ng K T
School of Psychology, La Trobe University, Bundoora, Victoria, Australia.
Neurobiol Learn Mem. 1995 Sep;64(2):106-18. doi: 10.1006/nlme.1995.1049.
There is substantial evidence that protein kinases, through the phosphorylation of substrate proteins, play a significant role in information processing in the brain, including processes underlying memory formation. Inhibition of the activity of the cyclic-adenosine monophosphate-dependent protein kinase A by the highly specific inhibitor, halofantrine, resulted in impairment of memory formation in day-old chicks trained on a single-trial passive avoidance task. A dose of 9.6 ng/chick halofantrine induced amnesia at the beginning of a protein synthesis-dependent long-term memory stage, the last of three stages of memory postulated to underly memory formation in the chick following passive avoidance learning. The concentration of halofantrine required for 50% inhibition of chick brain protein kinase A was found to be similar to that observed for bovine heart and rat liver. The amnestic effect of halofantrine is tentatively attributed to interference with de novo protein synthesis necessary for long-term memory consolidation. Neither anthraquinone nor the anthraquinone derivative anthraflavic acid, which have little effect on protein kinase A activity, affected memory retention. On the other hand, two other anthraquinone derivatives, chrysophanic acid and purpurin, which inhibit PKA activity, at doses of 0.25 and 0.5 ng/chick also yielded retention deficits. In these cases, however, retention losses occurred earlier than observed with halofantrine, at about 30 min post-training. The earlier effects of these inhibitors may be due to the additional inhibitory action of these compounds on protein kinase C activity, which has been demonstrated in previous studies to be implicated, possibly through phosphorylation of the GAP43 phosphoprotein, in memory processing in the stage of memory immediately preceding the protein synthesis-dependent long-term stage.
有大量证据表明，蛋白激酶通过对底物蛋白进行磷酸化，在大脑的信息处理中发挥重要作用，包括在记忆形成的潜在过程中。高特异性抑制剂卤泛群对环磷酸腺苷依赖性蛋白激酶A活性的抑制，导致了在单次被动回避任务训练的一日龄雏鸡中记忆形成受损。剂量为9.6纳克/只的卤泛群在蛋白质合成依赖性长期记忆阶段开始时诱发失忆，这是被动回避学习后雏鸡记忆形成所假定的三个记忆阶段中的最后一个阶段。发现50%抑制雏鸡脑蛋白激酶A所需的卤泛群浓度与牛心和大鼠肝脏中观察到的浓度相似。卤泛群的失忆效应初步归因于对长期记忆巩固所需的从头蛋白质合成的干扰。对蛋白激酶A活性几乎没有影响的蒽醌和蒽醌衍生物蒽黄酮酸均未影响记忆保持。另一方面，另外两种抑制PKA活性的蒽醌衍生物，大黄酸和紫红素，剂量为0.25和0.5纳克/只时也导致了记忆保持缺陷。然而，在这些情况下，记忆保持损失比卤泛群观察到的更早出现，在训练后约30分钟。这些抑制剂的早期效应可能是由于这些化合物对蛋白激酶C活性的额外抑制作用，先前的研究已经证明，蛋白激酶C活性可能通过GAP43磷蛋白的磷酸化，参与了在蛋白质合成依赖性长期阶段之前的记忆阶段的记忆处理。
