Fibroblast growth factor 8 regulates postnatal development of paraventricular nucleus neuroendocrine cells.
Fibroblast growth factor 8 regulates postnatal development of paraventricular nucleus neuroendocrine cells.
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DOI：
10.1186/s12993-015-0081-9
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发表时间：
2015-11-04
期刊：
影响因子：
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通讯作者：
Chung WC
中科院分区：
文献类型：
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作者：
Rodriguez KM;Stevenson EL;Stewart CE;Linscott ML;Chung WC
成纤维细胞生长因子（FGF）是指导脊椎动物脑发育的重要信号分子。特别是FGF 8基因信号传导可能对下丘脑-垂体-肾上腺（HPA）轴的发育很重要。事实上，新生的Fgf 8低形态小鼠在室旁核（PVN）（HPA轴的中枢输出成分）中的血管加压素（VP）神经元数量显著减少。此外，最近的研究表明，成年杂合（+/neo）Fgf 8亚型小鼠表现出更多的焦虑样行为比野生型（WT）小鼠。这些研究使我们调查是否FGF 8亚型废除VP和/或促肾上腺皮质激素释放激素（CRH）的神经元发育在出生后第21天（PN）和成年小鼠PVN。此外，我们研究了Fgf 8亚型是否破坏这些小鼠的HPA反应性。使用免疫组织化学，我们研究了VP和CRH神经元位于PVN的PN 21和成年Fgf 8 +/neo小鼠的发展。此外，我们使用了束缚应激（RS）的范例，并测量皮质酮水平与酶免疫测定，以评估HPA轴激活。在PN 21和成年期，WT和Fgf 8 +/neo小鼠之间PVN中VP神经元的数量没有差异。相反，PN 21时，Fgf 8 +/neo小鼠中的CRH免疫反应性远高于WT小鼠，成年小鼠中不再显示该差异。15 min后，RS引起成年Fgf 8 +/neo小鼠皮质酮水平的增加高于WT小鼠，但45 min后未见差异。首先，Fgf 8亚型没有消除小鼠PVN中的VP和CRH神经元，而是破坏了PVN神经元中神经肽表达开始的出生后时间。第二，Fgf 8的低型性可能，在某种程度上，是一种解释情感障碍，涉及HPA轴的过度活跃，如焦虑。
Fibroblast growth factors (FGFs) are crucial signaling molecules that direct the development of the vertebrate brain. FGF8 gene signaling in particular, may be important for the development of the hypothalamus–pituitary–adrenal (HPA)-axis. Indeed, newborn Fgf8 hypomorphic mice harbor a major reduction in the number of vasopressin (VP) neurons in the paraventricular nucleus (PVN), the central output component of the HPA-axis. Additionally, recent studies indicated that adult heterozygous (+/neo) Fgf8 hypomorphic mice exhibit more anxiety-like behaviors than wildtype (WT) mice. These studies led us to investigate whether Fgf8 hypomorphy abrogated VP and/or corticotropin-releasing hormone (CRH) neuronal development in the postnatal day (PN) 21 and adult mouse PVN. Furthermore, we studied whether Fgf8 hypomorphy disrupted HPA responsiveness in these mice. Using immunohistochemistry, we examined the development of VP and CRH neurons located in the PVN of PN 21 and adult Fgf8+/neo mice. Moreover, we used a restraint stress (RS) paradigm and measured corticosterone levels with enzyme immunoassays in order to assess HPA axis activation. The number of VP neurons in the PVN did not differ between WT and Fgf8+/neo mice on PN 21 and in adulthood. In contrast, CRH immunoreactivity was much higher in Fgf8+/neo mice than in WT mice on PN 21, this difference was no longer shown in adult mice. RS caused a higher increase in corticosterone levels in adult Fgf8+/neo mice than in WT mice after 15 min, but no difference was seen after 45 min. First, Fgf8 hypomorphy did not eliminate VP and CRH neurons in the mouse PVN, but rather disrupted the postnatal timing of neuropeptide expression onset in PVN neurons. Second, Fgf8 hypomorphy may, in part, be an explanation for affective disorders involving hyperactivity of the HPA axis, such as anxiety.