Mouse behavioral endophenotypes for schizophrenia
Mouse behavioral endophenotypes for schizophrenia
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DOI：
10.1016/j.brainresbull.2010.04.008
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发表时间：
2010-09-30
影响因子：
3.8
通讯作者：
Siegel, Steven J.
中科院分区：
文献类型：
--
作者：
Amann, Laura C.;Gandal, Michael J.;Siegel, Steven J.
内表型是一种可遗传的特征，通常被认为与基于基因的神经缺陷的相关性比疾病表型本身更高。因此，在疾病患者未受影响的亲属中可能会观察到内表型缺陷。一旦确定了特定疾病的内表型，如精神分裂症，就可以建立作用机制，并开发治疗方案，以便针对这些措施。本文描述和评估了利用精神分裂症小鼠的行为和电生理内表型的优点和局限性，这些内表型缺陷包括听觉事件相关电位(ERP)幅度和门控(特别是P20、N40、P80和P120)的降低。失配负性受损(MMN)、θ和伽马频率改变、分析、脉冲前抑制(PPI)降低、工作记忆和情景记忆受损(例如，新物体识别[NOR]、上下文和线索恐惧条件作用、潜伏抑制。莫里斯和，放射臂迷宫识别和戳鼻子)：社交；和运动活动。包括氯胺酮、MK-801和苯环利定(PCP)在内的各种药理治疗可以用来诱导上述一些缺陷，许多转基因小鼠已经被开发出来，以解决导致这种内表型差异的机制。我们还讨论了使用这些措施的可行性和有效性，以及它们潜在的临床意义。并提出了一些可以提高先期数据可译性的做法。(C)2010 Elsevier Inc.保留所有权利。
An endophenotype is a heritable trait that is generally considered to be more highly, associated with a gene-based neurological deficit than a disease phenotype itself Such. endophenotypic deficits may therefore be observed in the non-affected relatives of disease patients. Once endophenotypes have been established for a given illness, such as schizophrenia, mechanisms of, action may then be established and treatment options developed in order to target such measures. The, current paper describes and assesses the merits and limitations of utilizing behavioral and, electrophysiological endophenotypes of schizophrenia in mice Such endophenotypic deficits include, decreased auditory event related potential (ERP) amplitude and gating (specifically, that of the P20, N40, P80 and P120). Impaired mismatch negativity (MMN), changes in theta and gamma frequency, analyses, decreased pre-pulse inhibition (PPI), impaired working and episodic memories (for instance, novel object recognition [NOR], contextual and cued fear conditioning, latent inhibition. Morris and, radial arm maze identification and nose poke): sociability; and locomotor activity. A variety of, pharmacological treatments, including ketamine, MK-801 and phencyclidine (PCP) can be used to, induce some of the deficits described above, and numerous transgenic mouse strains have been, developed to address the mechanisms responsible for such endophenotypic differences. We also, address the viability and validity of using such measures regarding their potential clinical implications. and suggest several practices that could increase the translatability of prechnical data. (C) 2010 Elsevier Inc. All rights reserved.