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缺乏富含纹状体的蛋白酪氨酸磷酸酶时的社会记忆和社会模式改变

Social Memory and Social Patterns Alterations in the Absence of STriatal-Enriched Protein Tyrosine Phosphatase.

作者信息

Blázquez Gloria, Castañé Anna, Saavedra Ana, Masana Mercè, Alberch Jordi, Pérez-Navarro Esther

机构信息

Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

出版信息

Front Behav Neurosci. 2019 Jan 25;12:317. doi: 10.3389/fnbeh.2018.00317. eCollection 2018.

Abstract

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a neural-specific protein that opposes the development of synaptic strengthening and whose levels are altered in several neurodegenerative and psychiatric disorders. Since STEP is expressed in brain regions implicated in social behavior, namely the striatum, the CA2 region of the hippocampus, cortex and amygdala, here we investigated whether social memory and social patterns were altered in STEP knockout (KO) mice. Our data robustly demonstrated that STEP KO mice presented specific social memory impairment as indicated by the three-chamber sociability test, the social discrimination test, the 11-trial habituation/dishabituation social recognition test, and the novel object recognition test (NORT). This affectation was not related to deficiencies in the detection of social olfactory cues, altered sociability or anxiety levels. However, STEP KO mice showed lower exploratory activity, reduced interaction time with an intruder, less dominant behavior and higher immobility time in the tail suspension test than controls, suggesting alterations in motivation. Moreover, the extracellular levels of dopamine (DA), but not serotonin (5-HT), were increased in the dorsal striatum of STEP KO mice. Overall, our results indicate that STEP deficiency disrupts social memory and other social behaviors as well as DA homeostasis in the dorsal striatum.

摘要

富含纹状体蛋白酪氨酸磷酸酶(STEP)是一种神经特异性蛋白,它会抑制突触强化的发展,并且其水平在几种神经退行性疾病和精神疾病中会发生改变。由于STEP在与社会行为相关的脑区表达,即纹状体、海马体的CA2区、皮质和杏仁核,因此我们在此研究了STEP基因敲除(KO)小鼠的社会记忆和社会模式是否发生改变。我们的数据有力地证明,通过三室社交性测试、社会辨别测试、11次试验的习惯化/去习惯化社会识别测试和新物体识别测试(NORT)表明,STEP KO小鼠存在特定的社会记忆障碍。这种影响与社会嗅觉线索检测缺陷、社交性改变或焦虑水平无关。然而,与对照组相比,STEP KO小鼠在悬尾试验中表现出较低的探索活动、与入侵者的互动时间减少、支配行为减少以及不动时间增加,这表明动机发生了改变。此外,STEP KO小鼠背侧纹状体中多巴胺(DA)的细胞外水平升高,但血清素(5-HT)的水平未升高。总体而言,我们的结果表明,STEP缺乏会破坏社会记忆和其他社会行为以及背侧纹状体中的DA稳态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a52/6362413/919ccbc65c10/fnbeh-12-00317-g0001.jpg

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