Decreased cognitive function of ALG13KO female mice may be related to the decreased plasticity of hippocampal neurons

Decreased cognitive function of ALG13KO female mice may be related to the decreased plasticity of hippocampal neurons
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DOI:
10.1016/j.npep.2022.102290
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发表时间:
2022-09-21
期刊:
影响因子:
2.9
通讯作者:
Sun, Tao
Sun, Tao
中科院分区:
医学3区
文献类型:
--
作者:
Guo, Baorui;Xia, Yu;Sun, Tao

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天冬酰胺连接糖基化 13 (ALG13) 是一种 X 连锁基因,编码参与 N 末端糖基化的蛋白质。 ALG13 缺乏会导致 ALG13 先天性糖基化障碍 (ALG13-CDG),通常发生在女性中,表现为智力低下和癫痫。认知功能是海马体的一项重要功能,是学习、记忆和社交能力的基础。然而,研究人员尚未研究ALG13对海马认知功能的影响。在这项研究中,ALG13敲除(KO)雌性小鼠的探索、学习、记忆和社交能力在行为实验中均有所下降。高尔基体染色显示海马神经元的复杂性降低。突触可塑性因子突触后密度蛋白 95 (PSD95) 和突触素 (SYP) 的蛋白质印迹和免疫荧光染色显示出不同程度的下降。换句话说,ALG13的敲除可能降低了雌性小鼠海马中PSD95和SYP的表达。此外,它可能降低了海马各区域的突触可塑性,从而导致树突长度、复杂性和树突棘密度减少,从而影响海马功能并降低雌性小鼠的认知功能。
Asparagine-linked glycosylation 13 (ALG13) is an X-linked gene that encodes a protein involved in the glyco-sylation of the N-terminus. ALG13 deficiency leads to ALG13-congenital disorders of glycosylation (ALG13-CDG), usually in females presenting with mental retardation and epilepsy. Cognitive function is an important function of the hippocampus, and forms the basis for learning, memory and social abilities. However, researchers have not yet investigated the effect of ALG13 on hippocampal cognitive function. In this study, the exploration, learning, memory and social abilities of ALG13 knockout (KO) female mice were decreased in behavioral experiments. Golgi staining demonstrated a decrease in the complexity of hippocampal neurons. Western blot and immuno-fluorescence staining of the synaptic plasticity factors postsynaptic density protein 95 (PSD95) and synapto-physin (SYP) displayed varying degrees of decline. In other words, the KO of ALG13 may have reduced the expression of PSD95 and SYP in the hippocampus of female mice. Moreover, it may have lowered the synaptic plasticity in various areas of the hippocampus, thus resulting in decreased dendrite length, complexity, and dendrite spine density, which affected the hippocampal function and reduced the cognitive function in female mice.