Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase
Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase
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DOI：
10.1016/j.neuroscience.2008.07.006
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发表时间：
2008-09-09
期刊：
影响因子：
3.3
通讯作者：
Waddington, J. L.
中科院分区：
文献类型：
--
作者：
Babovic, D.;O'Tuathaigh, C. M.;Waddington, J. L.
儿茶酚-O-甲基转移酶是多巴胺代谢过程中的一种重要酶，也是精神分裂症患者前额叶皮层多巴胺依赖的工作记忆的重要调节因子。这项研究调查了儿茶酚-O-甲基转移酶基因杂合缺失和纯合子敲除小鼠的表型，研究了与精神病相关的过程。纯合子受试者在即刻空间工作记忆指标--自发交替中的表现有所改善；这种影响在男性中更为显著，并反映在空间学习/记忆指标--巴恩斯迷宫的某些方面。杂合子受试者在物体识别方面表现明显受损，这是一种识别记忆的指标；这种影响在保持时间间隔为5分钟的男性和女性中都很明显，但在男性中表现得更持久。在社交能力或社会新颖性偏好方面，任何一种基因都没有实质性的影响。儿茶酚-O-甲基转移酶纯合子缺失可改善空间学习/工作记忆，但对社会行为影响不大，杂合子缺失可导致再认记忆障碍。我们最近使用类似的方法报道，精神分裂症风险基因neuRegin-1缺失的小鼠有证据表明，神经调节蛋白-1缺失会扰乱社会行为，而对空间学习/工作记忆几乎没有影响。这些数据表明，儿茶酚-O-甲基转移酶和神经调节蛋白-1可能分别主要影响整个精神分裂症综合征的认知和社会内表型。(C)2008年IBRO。爱思唯尔有限公司出版。版权所有。
Catechol-O-methyltransferase is an important enzyme in the metabolism of dopamine and an important regulator of aspects of dopamine-dependent working memory in prefrontal cortex that are disturbed in schizophrenia. This study investigated the phenotype of mice with heterozygous deletion vs. homozygous knockout of the catechol-O-methyltransferase gene across paradigms that access processes relevant for psychotic illness. Homozygotes evidenced improved performance in spontaneous alternation, an index of immediate spatial working memory; this effect appeared more substantive in males and was reflected in performance in aspects of the Barnes maze, an index of spatial learning/memory. Heterozygotes evidenced impaired performance in object recognition, an index of recognition memory; this effect was evident for both sexes at a retention interval of 5 min but appeared more enduring in males. There were no material effects for either genotype in relation to sociability or social novelty preference. While homozygous catechol-O-methyltransferase deletion results in improvement in spatial learning/working memory with little effect on social behavior, heterozygous deletion results in impairment of recognition memory. We have reported recently, using similar methods, that mice with deletion of the schizophrenia risk gene neuregulin-1 evidence disruption to social behavior, with little effect on spatial learning/working memory. The data suggest that catechol-O-methyltransferase and neuregulin-1 may influence, respectively, primarily cognitive and social endophenotypes of the overall schizophrenia syndrome. (C) 2008 IBRO. published by Elsevier Ltd. All rights reserved.