Saitoh Yuko, Matsui Fumiko, Chiba Yoichi, Kawamura Noriko, Keino Hiromi, Satoh Mamoru, Kumagai Naoko, Ishii Sanae, Yoshikawa Keisuke, Shimada Atsuyoshi, Maeda Nobuaki, Oohira Atsuhiko, Hosokawa Masanori
Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan.
J Neurosci Res. 2008 May 1;86(6):1316-23. doi: 10.1002/jnr.21582.
The accelerated senescence-prone SAMP10 mouse strain is a model for age-dependent neurodegeneration and is characterized by brain atrophy and deficits in learning and memory. Because perineuronal nets play an important role in the synaptic plasticity of adult brains, we examined the distributions of molecules that constitute perineuronal nets in SAMP10 mouse brain samples and compared them with those in control SAMR1 mouse samples. Proteoglycan-related monoclonal antibody 6B4 (MAb6B4) clearly immunostained perineuronal nets in SAMR1 mice cortices, but the corresponding immunostaining in SAMP10 mice was very faint. MAb6B4 recognizes phosphacan/PTPzeta in immature brains. However, this antibody recognized several protein bands, including a 400-kDa core glycoprotein from chondroitin sulfate proteoglycan in homogenates of mature cortices from SAMR1 mice. The 400-kDa band was also recognized by antiaggrecan antibodies. The aggrecan core glycoprotein band was also detectable in samples from SAMP10 mice, but this glycoprotein was faintly immunostained by MAb6B4. Because MAb6B4 recognized the same set of protein bands that the monoclonal antibody Cat-315 recognized in mature cerebral cortices of SAMR1 mice, the MAb6B4 epitope appears to be closely related to that of Cat-315 and presumably represents a novel type of oligosaccharide that attaches to aggrecans. The Cat-315 epitope colocalized with aggrecan in perineuronal nets from SAMR1 mouse brain samples, whereas its expression was prominently reduced in SAMP10 mouse brain samples. The biological significance of the MAb6B4/Cat-315 epitope in brain function and its relationship to the neurodegeneration and learning disabilities observed in SAMP10 mice remain to be elucidated.
易加速衰老的SAMP10小鼠品系是年龄依赖性神经退行性变的模型，其特征为脑萎缩以及学习和记忆缺陷。由于神经元周围网在成年大脑的突触可塑性中起重要作用，我们检测了构成SAMP10小鼠脑样本中神经元周围网的分子分布，并将其与对照SAMR1小鼠样本中的分布进行比较。蛋白聚糖相关单克隆抗体6B4（MAb6B4）能清晰地对SAMR1小鼠皮质中的神经元周围网进行免疫染色，但在SAMP10小鼠中相应的免疫染色非常微弱。MAb6B4在未成熟大脑中识别磷酸聚糖/蛋白酪氨酸磷酸酶ζ。然而，该抗体识别了几条蛋白条带，包括来自SAMR1小鼠成熟皮质匀浆中硫酸软骨素蛋白聚糖的400 kDa核心糖蛋白。抗聚集蛋白聚糖抗体也识别400 kDa条带。在SAMP10小鼠的样本中也可检测到聚集蛋白聚糖核心糖蛋白条带，但该糖蛋白被MAb6B4微弱免疫染色。由于MAb6B4识别的蛋白条带与单克隆抗体Cat-315在SAMR1小鼠成熟大脑皮质中识别的相同，MAb6B4表位似乎与Cat-315的表位密切相关，可能代表一种附着于聚集蛋白聚糖的新型寡糖。Cat-315表位在SAMR1小鼠脑样本的神经元周围网中与聚集蛋白聚糖共定位，而其在SAMP10小鼠脑样本中的表达显著降低。MAb6B4/Cat-315表位在脑功能中的生物学意义及其与SAMP10小鼠中观察到的神经退行性变和学习障碍的关系仍有待阐明。
