Michalak Agnieszka, Biala Grazyna
Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodźki Street, 20-093 Lublin, Poland.
Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodźki Street, 20-093 Lublin, Poland.
Behav Brain Res. 2017 Jan 15;317:27-36. doi: 10.1016/j.bbr.2016.09.023. Epub 2016 Sep 12.
Long-term potentiation (LTP) and long-term depression (LTD) depend on specific postsynaptic Ca/calmodulin concentration. LTP results from Ca influx through the activated NMDA receptors or voltage-gated calcium channels (VGCCs) and is linked with activation of protein kinases including mitogen-activated protein kinase (MAPK). Weaker synaptic stimulation, as a result of low Ca influx, leads to activation of Ca/calmodulin-dependent phosphatase (calcineurin - CaN) and triggers LTD. Interestingly, both memory formation and drug addiction share similar neuroplastic changes. Nicotine, which is one of the most common addictive drugs, manifests its memory effects through nicotinic acetylcholine receptors (nAChRs). Because nAChRs may also gate Ca, it is suggested that calcium signaling pathways are involved in nicotine-induced memory effects. Within the scope of the study was to evaluate the importance of calcium homeostasis and protein kinase/phosphatase balance in nicotine-induced short- and long-term memory effects. To assess memory function in mice passive avoidance test was used. The presented results confirm that acute nicotine (0.1mg/kg) improves short- and long-term memory. Pretreatment with L-type VGCC blockers (amlodipine, nicardipine verapamil) increased nicotine-induced memory improvement in the context of short- and long-term memory. Pretreatment with FK-506 (a potent CaN inhibitor) enhanced short- but not long-term memory effects of nicotine, while SL-327 (a selective MAPK/ERK kinase inhibitor) attenuated both nicotine-induced short- and long-term memory improvement. Acute nicotine enhances both types of memory via L-type VGCC blockade and via ERK1/2 activation. Only short- but not long-term memory enhancement induced by nicotine is dependent on CaN inhibition.
长时程增强（LTP）和长时程抑制（LTD）取决于特定的突触后钙/钙调蛋白浓度。LTP源于通过激活的N-甲基-D-天冬氨酸受体（NMDA受体）或电压门控钙通道（VGCC）的钙内流，并与包括丝裂原活化蛋白激酶（MAPK）在内的蛋白激酶的激活有关。由于钙内流较少导致的较弱突触刺激会导致钙/钙调蛋白依赖性磷酸酶（钙调神经磷酸酶-CaN）的激活并引发LTD。有趣的是，记忆形成和药物成瘾都有相似的神经可塑性变化。尼古丁是最常见的成瘾性药物之一，它通过烟碱型乙酰胆碱受体（nAChRs）表现出其记忆效应。因为nAChRs也可能控制钙通道，所以有人认为钙信号通路参与了尼古丁诱导的记忆效应。本研究的目的是评估钙稳态和蛋白激酶/磷酸酶平衡在尼古丁诱导的短期和长期记忆效应中的重要性。为了评估小鼠的记忆功能，采用了被动回避试验。给出的结果证实，急性尼古丁（0.1mg/kg）可改善短期和长期记忆。用L型VGCC阻滞剂（氨氯地平、尼卡地平、维拉帕米）预处理可增强尼古丁在短期和长期记忆方面诱导的记忆改善。用FK-506（一种有效的CaN抑制剂）预处理可增强尼古丁的短期记忆效应，但不能增强长期记忆效应，而SL-327（一种选择性MAPK/ERK激酶抑制剂）可减弱尼古丁诱导的短期和长期记忆改善。急性尼古丁通过L型VGCC阻断和ERK1/2激活来增强两种类型的记忆。尼古丁诱导的记忆增强中，只有短期记忆增强依赖于CaN抑制，长期记忆增强则不然。
