IGFBP2 Plays an Essential Role in Cognitive Development during Early Life
IGFBP2 Plays an Essential Role in Cognitive Development during Early Life
复制标题
IGFBP2在生命早期的认知发展中发挥重要作用
DOI：
10.1002/advs.201901152
复制
发表时间：
2019-12-04
期刊：
影响因子：
15.1
通讯作者：
Chen, Xuequn
中科院分区：
文献类型：
--
作者：
Khan, Shumsuzzaman;Lu, Xinjiang;Chen, Xuequn
确定生命早期认知发展的潜在机制是一个关键目标。海马中胰岛素样生长因子结合蛋白2（IGFBP 2）的表达在新生儿发育期间增加，并且与学习和记忆相关，但因果关系尚未建立。这里，据报道，表达IGFBP 2的神经元和星形胶质细胞分布在整个海马体中。IGFBP 2增强对CA 1锥体神经元的兴奋性输入，促进内在兴奋性和尖峰传递，并以细胞类型特异性方式调节兴奋性突触的可塑性。它通过增强N-甲基-D-天冬氨酸（NMDA）受体依赖性兴奋性突触后电流（EPSC）促进长时程增强（LTP），并增强神经突增殖和伸长。igfbp 2的敲除减少锥体细胞和中间神经元的数量，损害LTP和认知表现，并减少锥体神经元的紧张性兴奋，这些神经元都被IGFBP 2拯救。结果提供了对IGFBP 2在早期生命认知中的需求的深入了解。
Identifying the mechanisms underlying cognitive development in early life is a critical objective. The expression of insulin-like growth factor binding protein 2 (IGFBP2) in the hippocampus increases during neonatal development and is associated with learning and memory, but a causal connection has not been established. Here, it is reported that neurons and astrocytes expressing IGFBP2 are distributed throughout the hippocampus. IGFBP2 enhances excitatory inputs onto CA1 pyramidal neurons, facilitating intrinsic excitability and spike transmission, and regulates plasticity at excitatory synapses in a cell-type specific manner. It facilitates long-term potentiation (LTP) by enhancing N-methyl-D-aspartate (NMDA) receptor-dependent excitatory postsynaptic current (EPSC), and enhances neurite proliferation and elongation. Knockout of igfbp2 reduces the numbers of pyramidal cells and interneurons, impairs LTP and cognitive performance, and reduces tonic excitation of pyramidal neurons that are all rescued by IGFBP2. The results provide insight into the requirement for IGFBP2 in cognition in early life.