Kang Dong Woo, Chung Yoon Hee, Lee Jae Chul, Bang Joon Seok, Kim Daejin, Kim Sung Su, Kim Kyung Yong, Lee Won Bok, Cha Choong Ik
Department of Anatomy, Seoul National University College of Medicine, Chongno-Gu, Seoul, Korea.
Ann Anat. 2008 Dec 20;190(6):502-9. doi: 10.1016/j.aanat.2008.08.001. Epub 2008 Aug 28.
In the present study, we used the SOD1(G93A) mutant transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical studies to investigate the changes of insulin-like growth factor-binding protein 4 (IGFBP4) in the central nervous system. Decreased expression of IGFBP4 was obvious in the cerebral cortex, hippocampus, cerebellar cortex and inferior olive of SOD1(G93A) transgenic mice. In the cerebral cortex, there was a significant decrease in IGFBP4 immunoreactivity in the pyramidal cells. In the hippocampal formation, IGFBP4 immunoreactivity was also decreased in the pyramidal cells of CA1-3 areas and the granule cells of dentate gyrus. In the cerebellar cortex, IGFBP4 immunoreactivity was prominent in the granular layer in wtSOD1 transgenic mice, compared to that in SOD1(G93A) transgenic mice. IGFBP4 immunoreactivity was decreased in the inferior olive of SOD1(G93A) transgenic mice. This study, showing decreased IGFBP4 in different brain regions of SOD1(G93A) transgenic mice, may provide clues to understanding the differential susceptibility of neural structures in ALS, suggesting a role of IGFBP4 in an abnormality of cognitive and/or motor function in ALS. The mechanisms and functional implications of these decreases require elucidation.
在本研究中，我们使用超氧化物歧化酶1（SOD1）（G93A）突变转基因小鼠作为肌萎缩侧索硬化症（ALS）的体内模型，并进行免疫组织化学研究，以调查胰岛素样生长因子结合蛋白4（IGFBP4）在中枢神经系统中的变化。在SOD1（G93A）转基因小鼠的大脑皮质、海马体、小脑皮质和下橄榄核中，IGFBP4的表达明显降低。在大脑皮质中，锥体细胞中的IGFBP4免疫反应性显著降低。在海马结构中，CA1 - 3区的锥体细胞和齿状回的颗粒细胞中的IGFBP4免疫反应性也降低。在小脑皮质中，与SOD1（G93A）转基因小鼠相比，野生型SOD1转基因小鼠颗粒层中的IGFBP4免疫反应性更明显。SOD1（G93A）转基因小鼠下橄榄核中的IGFBP4免疫反应性降低。本研究显示SOD1（G93A）转基因小鼠不同脑区的IGFBP4降低，可能为理解ALS中神经结构的不同易感性提供线索，提示IGFBP4在ALS认知和/或运动功能异常中的作用。这些降低的机制和功能意义需要阐明。
