Mizuno Makoto, Yamada Kiyofumi, Maekawa Naoya, Saito Kuniaki, Seishima Mitsuru, Nabeshima Toshitaka
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Japan.
Behav Brain Res. 2002 Jul 18;133(2):135-41. doi: 10.1016/s0166-4328(01)00470-3.
Regulation of gene transcription via the cyclic adenosine 3',5'-monophosphate (cAMP)-mediated second messenger pathway has been implicated in learning and memory. Although the cAMP response element-binding protein (CREB) is an important transcription factor involved in long-term memory, it remains to be determined whether the CREB-dependent events are attributed to spatial learning and memory in a radial arm maze. Here we demonstrate that cAMP-dependent protein kinase A (PKA) and CREB are activated in the course of spatial learning. The radial maze training in rats resulted in a significant increase in PKA and CREB phosphorylation in the hippocampus in the course of spatial learning, which was followed by spatial memory formation. On the other hand, neither the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) nor the mRNA level of brain-derived neurotrophic factor was significantly affected. These results suggest that activation of the PKA/CREB signaling pathway in the hippocampus plays an important role in spatial memory formation.
通过环磷酸腺苷（cAMP）介导的第二信使途径对基因转录的调控与学习和记忆有关。尽管cAMP反应元件结合蛋白（CREB）是参与长期记忆的重要转录因子，但CREB依赖性事件是否归因于放射状臂迷宫中的空间学习和记忆仍有待确定。在这里，我们证明cAMP依赖性蛋白激酶A（PKA）和CREB在空间学习过程中被激活。大鼠的放射状迷宫训练导致在空间学习过程中海马体中PKA和CREB磷酸化显著增加，随后形成空间记忆。另一方面，Ca2+/钙调蛋白依赖性蛋白激酶II（CaMKII）和细胞外信号调节激酶（ERK）的磷酸化以及脑源性神经营养因子的mRNA水平均未受到显著影响。这些结果表明，海马体中PKA/CREB信号通路的激活在空间记忆形成中起重要作用。
