Khan Shumsuzzaman, Lu Xinjiang, Huang Qingyao, Tang Jiawei, Weng Jian, Yang Zhi, Lv Minchao, Xu Xiaokang, Xia Fangyuan, Zhang Mengchen, Li Yi, Liu Shuangshuang, Leng Gareth, Spitzer Nicholas, Du Jizeng, Chen Xuequn
Institute of Neuroscience Department of Neurobiology, and Department of Neurology of Second Affiliated Hospital NHC and CAMS Key Laboratory of Medical Neurobiology Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou 310058 China.
Present address: Case Western Reserve University Cleveland Ohio USA.
Adv Sci (Weinh). 2019 Oct 14;6(23):1901152. doi: 10.1002/advs.201901152. eCollection 2019 Dec.
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 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.
确定生命早期认知发展的潜在机制是一个关键目标。胰岛素样生长因子结合蛋白2（IGFBP2）在海马体中的表达在新生儿发育过程中增加，且与学习和记忆相关，但尚未建立因果联系。在此，有报道称表达IGFBP2的神经元和星形胶质细胞分布于整个海马体。IGFBP2增强了对CA1锥体神经元的兴奋性输入，促进内在兴奋性和动作电位传递，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）来促进长时程增强（LTP），并促进神经突的增殖和伸长。敲除 会减少锥体细胞和中间神经元的数量，损害LTP和认知表现，并降低锥体神经元的紧张性兴奋，而这些均可被IGFBP2挽救。这些结果为了解生命早期认知中对IGFBP2的需求提供了见解。
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