Woo Ran-Sook, Lee Ji-Hye, Yu Ha-Nul, Song Dae-Yong, Baik Tai-Kyoung
Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Korea.
Anat Cell Biol. 2011 Jun;44(2):116-27. doi: 10.5115/acb.2011.44.2.116. Epub 2011 Jun 30.
Neuregulin-1 (NRG1) plays important roles in the development and plasticity of the brain, and has also been reported to exhibit potent neuroprotective properties. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its role in Alzheimer's disease (AD). AD is characterized by progressive impairment of cognition and behavioral disturbance that strongly correlate with degeneration and death of neurons in the cerebral cortex and limbic brain areas, such as the hippocampus and the amygdala. Here, we show that the ErbB4 and phospho-ErbB4 immunoreactivities were higher intensity in the neurons of the CA1-2 transitional field of AD brains as compared to age-matched controls. Also, ErbB4 expression was increased in the neurons of the cortico medial nucleus amygdala, human basal forebrain and superior frontal gyrus of AD brains. In cerebral cortex and hippocampus of amyloid precursor protein/presenilin 1 double transgenic mice, ErbB4 immunoreactivity significantly increased in comparison to age-matched wild type control. These results suggest that up-regulating of ErbB4 immunoreactivity may involve in the progression of pathology of AD.
神经调节蛋白-1（NRG1）在大脑的发育和可塑性中发挥着重要作用，并且据报道还具有强大的神经保护特性。尽管关键的NRG1受体ErbB4在成年动物大脑的多个区域表达，但关于其在阿尔茨海默病（AD）中的作用却知之甚少。AD的特征是认知功能进行性受损和行为障碍，这与大脑皮质和边缘脑区（如海马体和杏仁核）中神经元的退化和死亡密切相关。在此，我们表明，与年龄匹配的对照组相比，AD大脑CA1-2过渡区神经元中的ErbB4和磷酸化ErbB4免疫反应性强度更高。此外，AD大脑的杏仁核皮质内侧核、人类基底前脑和额上回的神经元中ErbB4表达增加。在淀粉样前体蛋白/早老素1双转基因小鼠的大脑皮质和海马体中，与年龄匹配的野生型对照相比，ErbB4免疫反应性显著增加。这些结果表明，ErbB4免疫反应性的上调可能参与了AD的病理进展。
