Gαo1和Gαo1/Gαo2缺失会对海马苔藓纤维束解剖结构和神经元形态发生产生不同影响。

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Markus Höltje, Anton Wolkowicz, Irene Brunk, Jens Baron, Gudrun Ahnert-Hilger
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引用次数: 0

摘要

异三聚体G蛋白αo亚基在中枢神经系统中以两种剪接变体Gαo1和Gαo2的形式普遍表达,调控着大脑的各种功能。在这里,我们研究了单Gαo1、Gαo2和双Gαo1/2敲除对小鼠苔藓纤维束(海马连接回路的中心通路)出生后发育的影响。在小鼠出生后第2、4、8、12、16天和成年后,通过对囊泡锌转运体3(ZnT3)或突触素进行免疫组化染色,分析了苔藓纤维束覆盖的海马突触终止区的大小以及苔藓纤维束的各种纤维长度参数。最终,Gαo1基因敲除导致突触苔藓纤维末端场的发育生长在成年后的透明层中减少了37%,苔藓纤维束的总大小减少了30%。其他形态学参数,如束下锥体束的投射长度也有所增加(Gαo1 -/-小鼠的投射长度增加了52%)。相比之下,Gαo2基因敲除对苔藓纤维束没有影响。此外,通过使用原代杂合和同源Gαo1基因敲除的海马培养物,我们检测到同源基因敲除小鼠的轴突和树突长度(分别为-50%和-38%)以及轴突和树突分枝复杂性(分别为-75%和-72%的分枝结点)均明显下降。删除两个剪接变体 Gαo1 和 Gαo2 部分挽救了体内效应,并完全恢复了体外效应,这表明两个 Gαo 剪接变体对神经元发育和突触连接具有相反的功能相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
o1 and Gαo1/Gαo2 deletion differentially affect hippocampal mossy fiber tract anatomy and neuronal morphogenesis.

The heterotrimeric G-protein αo subunit is ubiquitously expressed in the CNS as two splice variants Gαo1 and Gαo2, regulating various brain functions. Here, we investigated the effect of single Gαo1, Gαo2, and double Gαo1/2 knockout on the postnatal development of the murine mossy fiber tract, a central pathway of the hippocampal connectivity circuit. The size of the hippocampal synaptic termination fields covered by mossy fiber boutons together with various fiber length parameters of the tract was analyzed by immunohistochemical staining of the vesicular Zinc transporter 3 (ZnT3) or Synaptoporin at postnatal days 2, 4, 8, 12, 16, and in the adult. Ultimately, Gαo1 knockout resulted in a reduced developmental growth of synaptic mossy fiber terminal fields by 37% in the adult Stratum lucidum and by 30% in the total mossy fiber tract size. Other morphological parameters such as projection length of the infrapyramidal bundle of the tract were increased (+52% in Gαo1 -/- mice). In contrast, Gαo2 knockout had no effects on the mossy fiber tract. Moreover, by using primary heterozygous and homozygous Gαo1 knockout hippocampal cultures, we detected a strongly pronounced reduction in axon and dendrite length (-50% and -38%, respectively) as well as axon and dendrite arborization complexity (-75% and -72% branch nodes, respectively) in the homozygous knockout. Deletion of both splice variants Gαo1 and Gαo2 partially rescued the in vivo and completely reconstituted the in vitro effects, indicating an opposing functional relevance of the two Gαo splice variants for neuronal development and synaptic connectivity.

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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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