Inhibition of PirB Activity by TAT-PEP Improves Mouse Motor Ability and Cognitive Behavior.
Inhibition of PirB Activity by TAT-PEP Improves Mouse Motor Ability and Cognitive Behavior.
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TAT-PEP 抑制 PirB 活性可改善小鼠运动能力和认知行为
DOI：
10.3389/fnagi.2017.00199
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发表时间：
2017
影响因子：
4.8
通讯作者：
Gou XC
中科院分区：
文献类型：
--
作者：
Mi YJ;Chen H;Guo N;Sun MY;Zhao ZH;Gao XC;Wang XL;Zhang RS;Zhou JB;Gou XC
配对免疫球蛋白样受体B(PirB)是髓鞘相关抑制蛋白的功能性受体，在脑损伤后轴突再生中发挥重要作用。然而，它在正常大脑功能随年龄增长中的作用以前还没有被研究过。因此，在本研究中，我们检测了1月龄、3月龄和18月龄小鼠大脑皮质、海马体和小脑中PirB的表达水平。结果表明，PirB的表达随着年龄的增长而增加。我们进一步证明，PirB的过表达抑制了PC12细胞中突起的生长，这种抑制活性可以被TAT-PEP逆转，TAT-PEP是一种融合了TAT结构域的重组可溶性PirB胞外结构域，用于穿透血脑屏障。体内实验表明，腹腔注射TAT-PEP可提高小鼠的运动能力和空间学习记忆能力，这可能是通过调节脑源性神经营养因子(BDNF)的分泌实现的。我们的研究表明，PirB与衰老有关，TAT-PEP可能是一种有希望的治疗药物，用于调节与年龄相关的运动和认知功能障碍。
Paired immunoglobulin-like receptor B (PirB), a functional receptor for myelin-associated inhibitory proteins, plays an important role in axon regeneration in injured brains. However, its role in normal brain function with age has not been previously investigated. Therefore in this study, we examined the expression level of PirB in the cerebral cortex, hippocampus and cerebellum of mice at 1 month, 3 months and 18 months of age. The results showed that the expression of PirB increased with age. We further demonstrated that overexpression of PirB inhibited neurite outgrowth in PC12 cells, and this inhibitory activity of PirB could be reversed by TAT-PEP, which is a recombinant soluble PirB ectodomain fused with TAT domain for blood-brain barrier penetration. In vivo study, intraperitoneal administration of TAT-PEP was capable of enhancing motor capacity and spatial learning and memory in mice, which appeared to be mediated through regulation of brain-derived neurotrophic factor (BDNF) secretion. Our study suggests that PirB is associated with aging and TAT-PEP may be a promising therapeutic agent for modulation of age-related motor and cognitive dysfunctions.