Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Neurochem Res. 2017 Dec;42(12):3465-3473. doi: 10.1007/s11064-017-2394-6. Epub 2017 Aug 29.
Previous proteome analysis studies from other groups have shown that cAST might be secreted from neurons and that cAST was detected in human cerebrospinal fluid. However, none of these studies focused on its role or significance. We therefore investigated the role of extracellular cAST for neurons. cAST was detected in conditioned medium from cultured cortical neurons, but not in fresh medium. Recombinant cAST treatment of cortical neurons significantly extended axonal length. Continuous intracerebroventricular administration of recombinant cAST in normal mice for 14 days significantly enhanced object recognition ability. In the brains of those mice, axonal densities and c-Fos expression levels were enhanced, especially in the perirhinal cortex, which mainly relates to object recognition memory. The present study found, for the first time, that extracellular cAST promoted axonal growth function in neurons and activated memory function. These findings indicate a new function of extracellular cAST and may drive the establishment of new therapeutic strategies for cognitive dysfunction. The present study found, for the first time, that extracellular cAST promotes axonal growth in neurons.
先前来自其他团队的蛋白质组分析研究表明，cAST 可能从神经元中分泌出来，并且在人脑脊液中检测到 cAST。然而，这些研究都没有关注其作用或意义。因此，我们研究了细胞外 cAST 对神经元的作用。在培养的皮质神经元的条件培养基中检测到 cAST，但在新鲜培养基中未检测到。重组 cAST 处理皮质神经元显著延长了轴突长度。在正常小鼠中连续 14 天脑室内给予重组 cAST 可显著增强物体识别能力。在这些小鼠的大脑中，轴突密度和 c-Fos 表达水平增强，特别是在与物体识别记忆相关的边缘皮层。本研究首次发现，细胞外 cAST 可促进神经元中的轴突生长功能，并激活记忆功能。这些发现表明细胞外 cAST 具有新的功能，可能为认知功能障碍的治疗策略的建立提供依据。
