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α钙/钙调蛋白依赖性蛋白激酶II的自磷酸化影响小鼠的社交互动。

Autophosphorylation of αCaMKII affects social interactions in mice.

作者信息

Harda Z, Dzik J M, Nalberczak-Skóra M, Meyza K, Łukasiewicz K, Łęski S, Radwanska K

机构信息

The Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.

出版信息

Genes Brain Behav. 2018 Jun;17(5):e12457. doi: 10.1111/gbb.12457. Epub 2018 Feb 14.

Abstract

The α-Ca /calmodulin-dependent protein kinase II (αCaMKII), a key regulator of the glutamatergic synapse, has been implicated in many psychiatric disorders characterized by social impairments. Here we tested whether autophosphorylation of αCaMKII at threonine 286, which prolongs the activity of the enzyme, affects social behaviors in mice. We observed that autophosphorylation-deficient (αCaMKII-T286A) mutant female mice showed abnormal social behaviors characterized by decreased social preference and interest in conspecifics of the same sex, as compared to their wild-type littermates. Moreover, we developed a mathematical approach to analyze social interactions in group-housed mice in the automated IntelliCages. Using this approach we observed that αCaMKII-T286A mutants show decreased levels of social interactions in a social group, as compared with WT mice. WT mice increased the frequency of close social interactions when learning about the location of the food reward. This phenomenon was absent in the mutants. Overall, our data indicates that autophosphorylation of αCaMKII affects social interactions.

摘要

α-钙/钙调蛋白依赖性蛋白激酶II(αCaMKII)是谷氨酸能突触的关键调节因子,与许多以社交障碍为特征的精神疾病有关。在此,我们测试了αCaMKII在苏氨酸286位点的自身磷酸化(该磷酸化可延长酶的活性)是否会影响小鼠的社交行为。我们观察到,与野生型同窝小鼠相比,自身磷酸化缺陷型(αCaMKII-T286A)突变雌性小鼠表现出异常的社交行为,其特征是对同性同种个体的社交偏好和兴趣降低。此外,我们开发了一种数学方法来分析自动智能笼中群居小鼠的社交互动。使用这种方法,我们观察到与野生型小鼠相比,αCaMKII-T286A突变体在社会群体中的社交互动水平降低。野生型小鼠在了解食物奖励位置时会增加亲密社交互动的频率。而突变体中不存在这种现象。总体而言,我们的数据表明αCaMKII的自身磷酸化会影响社交互动。

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