Kuroda Kumi O, Meaney Michael J, Uetani Noriko, Fortin Yannick, Ponton André, Kato Tadafumi
Laboratory for Molecular Dynamics of Mental Disorder, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
Mol Cell Neurosci. 2007 Oct;36(2):121-31. doi: 10.1016/j.mcn.2007.05.010. Epub 2007 Jul 21.
During mouse parental behavior, neurons in the dorsal medial preoptic area (MPOAd) are activated and express transcription factors such as c-Fos and FosB. FosB-knockout mice are reported to be defective in parental care. To clarify molecular signaling responsible for parental behavior, we investigated gene expression profiles in the MPOAd of parental versus nonparental mice. We identified upregulation of NGFI-B, SPRY1, and Rad in parental mice, together with c-Fos and FosB. A common inducer of these genes, the extracellular signal regulated kinase (ERK) was phosphorylated in MPOAd neurons upon pup exposure. Pharmacological blockade of ERK phosphorylation inhibited the FosB upregulation in MPOAd, and the initiation of pup retrieving in virgin female mice, but did not affect the established parenting in parous females. Furthermore, induction of SPRY1 and Rad was impaired in MPOAd of nonparental FosB-knockout mice. These results suggest the pivotal role of ERK-FosB signaling in the initiation of parental care.
在小鼠的亲代行为过程中，背内侧视前区（MPOAd）的神经元被激活，并表达诸如c-Fos和FosB等转录因子。据报道，FosB基因敲除小鼠在亲代抚育方面存在缺陷。为了阐明负责亲代行为的分子信号传导，我们研究了亲代小鼠与非亲代小鼠MPOAd中的基因表达谱。我们发现亲代小鼠中NGFI-B、SPRY1和Rad与c-Fos和FosB一起上调。这些基因的共同诱导因子细胞外信号调节激酶（ERK）在幼崽暴露后在MPOAd神经元中被磷酸化。ERK磷酸化的药理学阻断抑制了MPOAd中FosB的上调，以及未生育雌性小鼠幼崽取回行为的起始，但不影响经产雌性小鼠已建立的亲代行为。此外，非亲代FosB基因敲除小鼠的MPOAd中SPRY1和Rad的诱导受损。这些结果表明ERK-FosB信号传导在亲代抚育起始中起关键作用。
