Child Primary Care Department of Shanghai Children's Medical Center, Shanghai Jiao Tung University School of Medicine, Shanghai, China.
Behav Brain Res. 2010 Mar 5;207(2):458-65. doi: 10.1016/j.bbr.2009.10.033. Epub 2009 Nov 3.
Sensorimotor function is important for cognitive development; however, little experimental evidence exists to support this assumption. In this study we tested the hypothesis that altered cAMP response element binding (CREB) protein induction and activity-regulated cytoskeletal-associated gene (Arc) expression may underlie the suppression of hippocampal neurogenesis and memory impairment associated with early sensorimotor deprivation. Associated memory was evaluated in sensorimotor deprived (T) and sham operated (C) rats using a contextual fear-conditioning task. Hippocampal dentate gyrus (DG) neurogenesis was assessed by Brdu and NeuN labeling. Hippocampal DG CREB signaling was examined by measuring protein and mRNA levels of CREB and activity-regulated cytoskeletal-associated gene (Arc). Contextual freezing responses in the 1-day recall test were significantly lower in 25- and 35-day-old group T compared to C rats (P<0.01), indicating that hippocampal-dependent memory impairment was caused by early sensorimotor deprivation. Furthermore, group T rats exhibited significantly decreased CREB and Arc activation in the hippocampal DG at 25 and 35 days compared to in group C rats (P<0.01 for both). These changes may underlie decreased neurogenesis and impaired memory. No significant between groups differences were apparent in 45- and 60-day-old rats. These results suggest that early sensorimotor deprivation may alter CREB signaling, decrease Arc activation, suppress neurogenesis and ultimately impair memory.
感觉运动功能对认知发育很重要；然而，很少有实验证据支持这种假设。在这项研究中，我们检验了这样一个假设，即 cAMP 反应元件结合蛋白（CREB）诱导和活性调节细胞骨架相关基因（Arc）表达的改变可能是海马神经发生抑制和与早期感觉运动剥夺相关的记忆损伤的基础。使用情景性恐惧条件反射任务评估感觉运动剥夺（T）和假手术（C）大鼠的相关记忆。通过 Brdu 和 NeuN 标记评估海马齿状回（DG）神经发生。通过测量 CREB 和活性调节细胞骨架相关基因（Arc）的蛋白和 mRNA 水平来检查海马 DG 的 CREB 信号转导。在 1 天回忆测试中，25 天和 35 天龄的 T 组大鼠的情景性冻结反应明显低于 C 组大鼠（P<0.01），表明海马依赖性记忆损伤是由早期感觉运动剥夺引起的。此外，与 C 组大鼠相比，T 组大鼠在 25 天和 35 天的海马 DG 中表现出明显降低的 CREB 和 Arc 激活（均 P<0.01）。这些变化可能是神经发生减少和记忆受损的原因。在 45 天和 60 天龄的大鼠中，两组之间没有明显的差异。这些结果表明，早期感觉运动剥夺可能改变 CREB 信号转导，降低 Arc 激活，抑制神经发生，最终损害记忆。
