Differential impact of polysialyltransferase ST8SiaII and ST8SiaIV knockout on social interaction and aggression
Differential impact of polysialyltransferase ST8SiaII and ST8SiaIV knockout on social interaction and aggression
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DOI：
10.1111/j.1601-183x.2010.00635.x
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发表时间：
2010-11-01
影响因子：
2.5
通讯作者：
Sandi, C.
中科院分区：
文献类型：
--
作者：
Calandreau, L.;Marquez, C.;Sandi, C.
先前对神经元细胞粘附分子(NCAM) -/-敲除（KO）小鼠的研究为NCAM在社会行为中的作用提供了证据。然而，NCAM最重要的翻译后修饰聚唾液酸（PSA）在这些小鼠中也不存在，这使得很难区分PSA或NCAM在社会互动中的特异性参与。为了解决这个问题，我们在一系列社会行为测试中评估了两种缺乏NCAM多唾液化所需的两种唾液转移酶之一的小鼠，唾液转移酶- x （St8SiaII或STX）和唾液转移酶（ST8SiaIV或PST）。结果显示，PST - KO小鼠的社交动机下降。这种缺陷部分可以用嗅觉缺陷来解释，并与分析的所有大脑区域（杏仁核、隔、终纹床核和额叶皮质）中PSA-NCAM表达的明显减少有关。STX KO小鼠表现出社会动机下降和攻击行为增加，这不能用嗅觉缺陷来解释。这一发现可能与在这些小鼠中观察到的减少焦虑样行为，增加运动和应激诱导的皮质酮分泌有关。此外，STX - KO小鼠的外侧隔和眶额皮质中PSA-NCAM表达轻度升高。总之，这些发现支持了PSA-NCAM在调节从缺乏社会动机到攻击性的社会行为中的作用。他们还强调STX KO小鼠是一种有趣的动物模型，它将暴力和多动的行为特征与减少的焦虑样行为结合起来。
Previous studies using neuronal cell adhesion molecule (NCAM) -/- knockout (KO) mice provided evidence for a role of NCAMs in social behaviors. However, polysialic acid (PSA), the most important post-translational modification of NCAM, was also absent in these mice, which makes it difficult to distinguish between the specific involvement of either PSA or NCAM in social interactions. To address this issue, we assessed two lines of mice deficient for one of the two sialyltransferase enzymes required for the polysialylation of NCAM, sialyltransferase-X (St8SiaII or STX) and polysialyltransferase (ST8SiaIV or PST), in a series of tests for social behaviors. Results showed that PST KO mice display a decreased motivation in social interaction. This deficit can be partly explained by olfactory deficits and was associated with a clear decrease in PSA-NCAM expression in all brain regions analyzed (amygdala, septum, bed nucleus of the stria terminalis and frontal cortices). STX KO mice displayed both a decreased social motivation and an increased aggressive behavior that cannot be explained by olfactory deficits. This finding might be related to the reduced anxiety-like behavior, increased locomotion and stress-induced corticosterone secretion observed in these mice. Moreover, STX KO mice showed mild increase of PSA-NCAM expression in the lateral septum and the orbitofrontal cortex. Altogether, these findings support a role for PSA-NCAM in the regulation of social behaviors ranging from a lack of social motivation to aggression. They also underscore STX KO mice as an interesting animal model that combines a behavioral profile of violence and hyperactivity with reduced anxiety-like behavior.