Neurobehavioral basis of the impaired nurturing in mice lacking the immediate early gene FosB
Neurobehavioral basis of the impaired nurturing in mice lacking the immediate early gene FosB
复制标题
DOI：
10.1016/j.brainres.2008.02.100
复制
发表时间：
2008-05-23
期刊：
影响因子：
2.9
通讯作者：
Kato, Tadafumi
中科院分区：
文献类型：
--
作者：
Kuroda, Kumi O.;Meaney, Michael J.;Kato, Tadafumi
转录因子FosB通过激活细胞外信号调节激酶（ERK）在育儿过程中诱导内侧视前区（MPOA）神经元中表达。FosB突变（-/-）产后小鼠和未交配的小鼠暴露于幼崽后表现出有缺陷的养育行为。FosB (-/-) MPOA不能完全上调ERK和钙信号的反馈调节因子SPRY1和Rad。本研究通过检测FosB（-/-）小鼠的基因表达谱和行为特征来研究FosB的功能。我们发现，与（+/）仔鼠相比，FosB（-/竖条-）仔鼠不仅表现出较少的亲代行为，而且也表现出较少的杀婴行为。然后，我们对FosB（-/-）小鼠的MPOA进行了基因表达分析，并与野生型幼崽进行了比较。我们发现FosB（-/-）小鼠MPOA中胶质纤维酸性蛋白（GFAP）、C4和Ela1 mRNA上调；所有这些基因产物都与一般的神经病理状况有关。免疫组织化学分析显示，GFAP的上调并不局限于MPOA，而是扩展到整个前脑，包括大脑皮层和纹状体。这种普遍的GFAP上调表明，FosB（-/-）小鼠可能存在除养育外的其他行为异常。事实上，这些老鼠在情绪上表现出明显的变化，这可以通过声音惊吓、升高的迷宫和被动回避测试来检测。这些结果表明，FosB（-/-）小鼠具有更广泛的神经行为功能障碍，这可能与培养缺陷有共同的机制。(C) 2008 Elsevier B.V.版权所有
The transcription factor FosB is induced in neurons of the medial preoptic area (MPOA) during parenting, through activation of the extracellular signal-regulated kinase (ERK). FosB mutant (-/-) postpartum mice and virgin mice that are exposed to pups show defective nurturing behavior. The FosB (-/-) MPOA fails to fully up-regulate SPRY1 and Rad, the feedback regulators of ERK and calcium signaling, respectively. Here we studied FosB function by examining the gene expression profiles and the behavioral characteristics of FosB (-/-) mice. We found that FosB (-/vertical bar-) mice exhibited not only decreased parenting but also decreased infanticide compared with (+/) littermates. We then performed gene expression analysis in the MPOA of FosB (-/-) mice compared with the wild-type littermates. We found up-regulation of glial fibrillary acidic protein (GFAP), C4, and Ela1 mRNA in the MPOA of FosB (-/-) mice; all of these gene products were implicated in general neuropathological conditions. Immunohistochemical analysis showed that up-regulation of GFAP was not restricted to MPOA but extended throughout the forebrain, including the cerebral cortex and striatum. Such pervasive GFAP up-regulation suggested that FosB (-/-) mice might have other behavioral abnormalities than nurturing. indeed, these mice showed a clear alteration in emotionality, detected by the acoustic startle, elevated plus maze, and passive avoidance tests. These results suggest that FosB (-/-) mice have broader neurobehavioral dysfunctions, with which the nurturing defect might share the common mechanism. (C) 2008 Elsevier B.V. All rights reserved.