Ishimoto Tetsuya, Ninomiya Kensuke, Inoue Ran, Koike Masato, Uchiyama Yasuo, Mori Hisashi
Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Glia. 2017 May;65(5):727-739. doi: 10.1002/glia.23129. Epub 2017 Feb 23.
The abnormal expression and function of myelin-related proteins contribute to nervous system dysfunction associated with neuropsychiatric disorders; however, the underlying mechanism of this remains unclear. We found here that breast carcinoma amplified sequence 1 (BCAS1), a basic protein abundant in the brain, was expressed specifically in oligodendrocytes and Schwann cells, and that its expression level was decreased by demyelination. This suggests that BCAS1 is a novel myelin-associated protein. BCAS1 knockout mice displayed schizophrenia-like behavioral abnormalities and a tendency toward reduced anxiety-like behaviors. Moreover, we found that the loss of BCAS1 specifically induced hypomyelination and the expression of inflammation-related genes in the brain. These observations provide a novel insight into the functional link between oligodendrocytes and inflammation and/or abnormal behaviors.
髓鞘相关蛋白的异常表达和功能导致了与神经精神疾病相关的神经系统功能障碍;然而,其潜在机制仍不清楚。我们在此发现,乳腺癌扩增序列1(BCAS1)是一种在脑中丰富的碱性蛋白,它在少突胶质细胞和施万细胞中特异性表达,并且其表达水平在脱髓鞘时降低。这表明BCAS1是一种新型的髓鞘相关蛋白。BCAS1基因敲除小鼠表现出精神分裂症样行为异常和焦虑样行为减少的倾向。此外,我们发现BCAS1的缺失特异性地诱导了脑内的髓鞘形成减少和炎症相关基因的表达。这些观察结果为少突胶质细胞与炎症和/或异常行为之间的功能联系提供了新的见解。