目的研究srGAP2(Slit-Robo GTPase activating Protein 2)、γ-氨基丁酸以及单核细胞趋化蛋白-1(MCP-1)在难治性癫痫患儿脑组织中的表达情况及意义。方法选取11例患儿的颞叶脑组织和同期11例正常标本的颞叶脑组织,使用免疫组化和免疫印...目的研究srGAP2(Slit-Robo GTPase activating Protein 2)、γ-氨基丁酸以及单核细胞趋化蛋白-1(MCP-1)在难治性癫痫患儿脑组织中的表达情况及意义。方法选取11例患儿的颞叶脑组织和同期11例正常标本的颞叶脑组织,使用免疫组化和免疫印迹等方法检测srGAP2、γ-氨基丁酸以及MCP-1的表达情况。结果难治性癫痫患儿脑组织中,srGAP2的阳性表达率显著高于正常脑组织。难治性癫痫患儿脑组织和正常脑组织可以看到染成棕褐色的神经元,但难治性癫痫患儿脑组织γ-氨基丁酸能神经元表达量明显低于正常脑组织。正常脑组织中MCP-1的表达较弱,而难治性癫痫患儿脑组织中MCP-1的表达较强。结论难治性癫痫患儿脑组织srGAP2和MCP-1表达上升而γ-氨基丁酸表达下降,srGAP2、γ-氨基丁酸及MCP-1与难治性癫痫发病密切相关,可能作为潜在治疗靶标。展开更多
The methylcytosine dioxygenases TET proteins （TET1, TET2, and TET3） play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro...The methylcytosine dioxygenases TET proteins （TET1, TET2, and TET3） play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA （valproic acid）-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neu- ronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demon- strated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells. Furthermore, we revealed that TET1 could positively regulate srGAP3 expression independent of its catalytic activity, and srGAP3 is required for TET-mediated neuronal differentiation of Neuro2a cells. The results presented here may facilitate better understanding of the role of TET proteins in neuronal differentiation, and provide a possible therapy target for neuroblastoma.展开更多
Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease rem...Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout(Srgap2+/–) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes(Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/– mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.展开更多
目的:srGAP2(Slit-Robo GTPase-activating protein 2)作为Slit-Robo下游信号通路中一个重要的RhoGAP分子,在大脑轴突的形成及神经细胞的迁移中发挥作用。本课题通过检测病人大脑组织中srGAP2的表达,从分子水平探讨srGAP2与难治性癫痫...目的:srGAP2(Slit-Robo GTPase-activating protein 2)作为Slit-Robo下游信号通路中一个重要的RhoGAP分子,在大脑轴突的形成及神经细胞的迁移中发挥作用。本课题通过检测病人大脑组织中srGAP2的表达,从分子水平探讨srGAP2与难治性癫痫发病机制的相关性。方法:从已建立的难治性癫痫脑库中随机选取35例患者的颞叶脑组织和同期15例相对正常的颞叶脑组织作为实验组与对照组。利用免疫组化,免疫荧光以及免疫印迹三种方法检测srGAP2在两组脑组织中的表达情况。结果:在正常人的颞叶脑组织中,srGAP2主要少量表达在神经元胞膜和胞浆中;而在难治性癫痫患者颞叶脑组织中srGAP2的表达量明显高于对照组(P<0.05)。结论:srGAP2可能与难治性癫痫的发生发展密切相关。展开更多
文摘目的研究srGAP2(Slit-Robo GTPase activating Protein 2)、γ-氨基丁酸以及单核细胞趋化蛋白-1(MCP-1)在难治性癫痫患儿脑组织中的表达情况及意义。方法选取11例患儿的颞叶脑组织和同期11例正常标本的颞叶脑组织,使用免疫组化和免疫印迹等方法检测srGAP2、γ-氨基丁酸以及MCP-1的表达情况。结果难治性癫痫患儿脑组织中,srGAP2的阳性表达率显著高于正常脑组织。难治性癫痫患儿脑组织和正常脑组织可以看到染成棕褐色的神经元,但难治性癫痫患儿脑组织γ-氨基丁酸能神经元表达量明显低于正常脑组织。正常脑组织中MCP-1的表达较弱,而难治性癫痫患儿脑组织中MCP-1的表达较强。结论难治性癫痫患儿脑组织srGAP2和MCP-1表达上升而γ-氨基丁酸表达下降,srGAP2、γ-氨基丁酸及MCP-1与难治性癫痫发病密切相关,可能作为潜在治疗靶标。
文摘The methylcytosine dioxygenases TET proteins （TET1, TET2, and TET3） play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA （valproic acid）-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neu- ronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demon- strated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells. Furthermore, we revealed that TET1 could positively regulate srGAP3 expression independent of its catalytic activity, and srGAP3 is required for TET-mediated neuronal differentiation of Neuro2a cells. The results presented here may facilitate better understanding of the role of TET proteins in neuronal differentiation, and provide a possible therapy target for neuroblastoma.
基金supported by the Notional Natural Science Foundation of China,Nos.81770918 (to ZLC),31871383 (to TL)the Natural Science Foundation of Zhejiang Province,No.LY16H120006 (to ZLC)the Departmental Funds from Wenzhou Medical University,No.89214018 (to ZLC)。
文摘Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout(Srgap2+/–) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes(Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/– mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.
文摘目的:srGAP2(Slit-Robo GTPase-activating protein 2)作为Slit-Robo下游信号通路中一个重要的RhoGAP分子,在大脑轴突的形成及神经细胞的迁移中发挥作用。本课题通过检测病人大脑组织中srGAP2的表达,从分子水平探讨srGAP2与难治性癫痫发病机制的相关性。方法:从已建立的难治性癫痫脑库中随机选取35例患者的颞叶脑组织和同期15例相对正常的颞叶脑组织作为实验组与对照组。利用免疫组化,免疫荧光以及免疫印迹三种方法检测srGAP2在两组脑组织中的表达情况。结果:在正常人的颞叶脑组织中,srGAP2主要少量表达在神经元胞膜和胞浆中;而在难治性癫痫患者颞叶脑组织中srGAP2的表达量明显高于对照组(P<0.05)。结论:srGAP2可能与难治性癫痫的发生发展密切相关。
