Mechawar N, Lacoste B, Yu W-F, Srivastava L K, Quirion R
Douglas Hospital Research Centre, McGill University, Department of Psychiatry, 6875 LaSalle Boulevard, Verdun, Montréal, Québec, Canada H4H 1R3.
Neuroscience. 2007 Aug 10;148(1):126-39. doi: 10.1016/j.neuroscience.2007.04.066. Epub 2007 Jul 16.
We investigated the cellular and subcellular distributions of neuregulin tyrosine kinase receptor ErbB4 in the postnatal rat frontal cortex and hippocampus by light-, confocal- and electron-microscopic immunocytochemistry. At birth, ErbB4-immunoreactivity (ErbB4-IR) was prominent in the apical cytoplasm and dendrites of cortical plate neurons and hippocampal pyramidal cells. Throughout postnatal development and in adulthood, ErbB4-IR in both regions remained confined to the somatodendritic compartment of neurons, which increased in number to reach the adult pattern by the end of the first postnatal month (P30). At all ages examined, double-labeling experiments revealed that ErbB4-IR always co-localized with the neuronal marker neuronal nuclei (NeuN) and never with glial markers Nestin or glial fibrillary acidic protein (GFAP). Immunoperoxidase labeling at the ultrastructural level confirmed the exclusive localization of ErbB4-IR in somatodendrites, and notably in dendritic spines. Immunogold labeling showed preponderant ErbB4-IR in the cytoplasm, where it was associated with microtubules. Furthermore, ErbB4-IR was abundant in the nucleus of adult cortical and hippocampal neurons, suggesting a role for ErbB4 nuclear signaling in the brain beyond embryonic development. Taken together, these results show that ErbB4 is expressed by neuronal somatodendrites in cerebral cortex and hippocampus from birth to adulthood, and support a role for neuregulins in dendritic growth and plasticity.
我们通过光镜、共聚焦显微镜和电子显微镜免疫细胞化学方法，研究了出生后大鼠额叶皮质和海马中神经调节蛋白酪氨酸激酶受体ErbB4的细胞和亚细胞分布。出生时，ErbB4免疫反应性（ErbB4-IR）在皮质板神经元和海马锥体细胞的顶端细胞质和树突中很突出。在出生后的整个发育过程以及成年期，这两个区域的ErbB4-IR都局限于神经元的胞体树突部分，其数量在出生后第一个月末（P30）增加并达到成年模式。在所有检查的年龄段，双重标记实验表明，ErbB4-IR总是与神经元标记物神经元细胞核（NeuN）共定位，而从不与神经胶质标记物巢蛋白或胶质纤维酸性蛋白（GFAP）共定位。超微结构水平的免疫过氧化物酶标记证实了ErbB4-IR仅定位于胞体树突，特别是树突棘中。免疫金标记显示，ErbB4-IR在细胞质中占优势，且与微管相关。此外，ErbB4-IR在成年皮质和海马神经元的细胞核中丰富，这表明ErbB4核信号在胚胎发育后的大脑中发挥作用。综上所述，这些结果表明，从出生到成年，ErbB4在大脑皮质和海马的神经元胞体树突中表达，并支持神经调节蛋白在树突生长和可塑性中的作用。
