Elucidation of mechanisms for spontaneous epileptic seizures in mice lacking μ3B, a subunit of the neuron-specific AP-3B complex

阐明缺乏 μ3B（神经元特异性 AP-3B 复合物的亚基）的小鼠自发性癫痫发作的机制

• 批准号: 15591208
• 负责人: MORI Fumiaki
• 金额: $ 2.24万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591208/
• 关键词: Epilepsy; Adaptor protein complex; μ3B; Synaptic vesicle formation; Hippocampus; Excitatory terminal; Inhibitory terminal; 抑制性終末; CA3

Adaptor protein (AP) complexes regulate the vesicular transport of cargo proteins in the late secretory and endocytic pathways. Mice lacking μ3B, a subunit of the neuron-specific AP-3B complex, suffered from spontaneous epileptic seizures after the age of 15 weeks.In 2003, we performed morphometrical examinations of the CA1 region in μ3B knockout mice (KO) and wild type mice (WT) at the ages of 2,4,6,8 and 16 weeks. Conventional histological examinations revealed no abnormality in KO. There was no difference in the sizes of synaptic boutons between KO and WT. However, the diameter of synaptic vesicles in inhibitory terminals in KO was smaller than that in WT at the ages of 2,4,6,8 and 16 weeks. The diameter of synaptic vesicles in excitatory terminals in KO was smaller than that in WT at the ages of 4,6 and 8 weeks, but not at the ages of 2 and 16 weeks. The densities of synaptic vesicles in both terminals in KO were lower than those in WT.In 2004, we performed morphometrical examinations of the CA3 region in μ3B knockout mice (KO) and wild type mice (WT) at the ages of 2,4,6,8 and 16 weeks. Conventional histological examinations revealed no abnormality in KO. There was no difference in the sizes of synaptic boutons between KO and WT. However, the diameter of synaptic vesicles in inhibitory terminals in KO was smaller than that in WT at the ages of 4,6,8 and 16 weeks, but not at the age of 2 weeks. On the other, the diameter of synaptic vesicles in mossy fiber terminals in KO was larger than that in WT at the ages of 2-16 weeks. The densities of synaptic vesicles in the mossy fiber terminals, but not the inhibitory, in KO were lower than those in WT.It is possible that the imbalance between excitatory and inhibitory inputs to the hippocampus evokes epileptic seizures in this model.

衔接蛋白（AP）复合物在晚期分泌和内吞途径中调节货物蛋白的囊泡转运。2003年，我们对μ 3B基因敲除小鼠（KO）和野生型小鼠（WT）在2、4、6、8和16周龄时海马CA 1区进行了形态计量学研究。常规组织学检查显示KO无异常。KO和WT的突触终扣大小无差异。KO组抑制性终末突触囊泡直径在2、4、6、8和16周龄均小于WT组。KO组兴奋性终末内突触囊泡直径在4、6、8周龄均小于WT组，而在2、16周龄则无显著差异。2004年我们对μ3B基因敲除小鼠（KO）和野生型小鼠（WT）在2、4、6、8和16周龄时海马CA 3区进行了形态计量学观察。常规组织学检查显示KO无异常。KO和WT的突触终扣大小无差异。KO组抑制性终末内突触囊泡直径在4、6、8、16周龄时均小于WT组，而在2周龄时则无明显变化。2-16周龄KO组苔藓纤维终末突触囊泡直径大于WT组。KO中苔藓纤维末端的突触囊泡密度低于WT中的突触囊泡密度，但抑制性突触囊泡密度不低于WT中的突触囊泡密度。在该模型中，海马兴奋性和抑制性输入之间的不平衡可能引起癫痫发作。

项目成果

Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epileptieus

兰尼碱受体激活对红藻氨酸诱导的癫痫持续状态后神经递质释放和神经元细胞死亡的影响

• 期刊: Epilepsy Res (in press)
• 作者: Mori F;et al.
• 通讯作者: et al.

Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.

缺乏AP-3B网格蛋白适配器的小鼠中含GABA的突触囊泡的功能不良。

• DOI: 10.1083/jcb.200405032
• 发表时间: 2004-10-25
• 期刊: JOURNAL OF CELL BIOLOGY
• 影响因子: 7.8
• 作者: Nakatsu, Fubito;Okada, Motohiro;Mori, Fumiaki;Kumazawa, Noriko;Iwasa, Hiroto;Zhu, Gang;Kasagi, Yasufumi;Kamiya, Haruyuki;Harada, Akihiro;Nishimura, Kazuhiro;Takeuchi, Arata;Miyazaki, Taisuke;Watanabe, Masahiko;Yuasa, Shigeki;Manabe, Toshiya;Wakabayashi, Koichi;Kaneko, Sunao;Saito, Takashi;Ohno, Hiroshi
• 通讯作者: Ohno, Hiroshi

Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epilepticus

• DOI: 10.1016/j.eplepsyres.2005.04.006
• 发表时间: 2005-06-01
• 期刊: EPILEPSY RESEARCH
• 影响因子: 2.2
• 作者: Mori, F;Okada, M;Wakabayashi, K
• 通讯作者: Wakabayashi, K