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Wnts在成年小鼠的脊髓中表达,并且在损伤后被差异性诱导。

Wnts are expressed in the spinal cord of adult mice and are differentially induced after injury.

作者信息

González-Fernández Carlos, Fernández-Martos Carmen María, Shields Shannon D, Arenas Ernest, Javier Rodríguez Francisco

机构信息

1 Molecular Neurology Laboratory, Hospital Nacional de Paraplejicos (HNP) , Toledo, Spain .

出版信息

J Neurotrauma. 2014 Mar 15;31(6):565-81. doi: 10.1089/neu.2013.3067.

Abstract

The Wnt family of proteins plays key roles during central nervous system development and has been involved in several neuropathologies during adulthood, including spinal cord injury (SCI). However, Wnts expression knowledge is relatively limited during adult stages. Here, we sought to define the Wnt family expression pattern after SCI in adult mice by using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Under physiological conditions, the messenger RNAs (mRNAs) of most Wnt ligands, inhibitors, receptors, and coreceptors are constitutively expressed in healthy adult mice. After dorsal hemisection, we found significant time-dependent variations, with a prominent up-regulation of Wnt inhibitory factor 1 (Wif1). IHC against Frizzled (Fz) 1 and Fz4, as representatives of late and acute up-regulated receptors, showed a differential expression in the uninjured spinal cord of Fz1 by neurons and oligodendrocytes and Fz4 by astrocytes. After injury, both receptors were maintained in the same type of cells. Finally, by using BATgal reporter mice, our results revealed active β-catenin signaling in neurons of the dorsal horn and cells of the central canal of uninjured spinal cords, besides a lack of additional SCI-induced activation. In conclusion, we demonstrate Wnt expression in the adult spinal cord of mice that is modulated by SCI, which differs from that previously described in rats. Further, Fz receptors are differentially expressed by neurons and glial cells, suggestive for cell-specific patterns and thus diverse physiological roles. Further studies will help toward in-depth characterization of the role of all Wnt factors and receptors described and eventually allow for the design of novel therapies.

摘要

Wnt蛋白家族在中枢神经系统发育过程中发挥着关键作用,并且在成年期参与了多种神经病理学过程,包括脊髓损伤(SCI)。然而,在成年阶段,Wnts的表达情况相对有限。在此,我们试图通过定量聚合酶链反应(qPCR)和免疫组织化学(IHC)来确定成年小鼠脊髓损伤后Wnt家族的表达模式。在生理条件下,大多数Wnt配体、抑制剂、受体和共受体的信使核糖核酸(mRNA)在健康成年小鼠中组成性表达。在背侧半横切后,我们发现了显著的时间依赖性变化,其中Wnt抑制因子1(Wif1)显著上调。针对卷曲蛋白(Fz)1和Fz4(作为晚期和急性上调受体的代表)的免疫组织化学显示,在未受伤的脊髓中,Fz1在神经元和少突胶质细胞中表达,Fz4在星形胶质细胞中表达,二者存在差异。损伤后,这两种受体在相同类型的细胞中持续表达。最后,通过使用BATgal报告基因小鼠,我们的结果显示,在未受伤脊髓的背角神经元和中央管细胞中存在活跃的β-连环蛋白信号传导,此外,脊髓损伤并未诱导额外的激活。总之,我们证明了小鼠成年脊髓中的Wnt表达受脊髓损伤调节,这与先前在大鼠中描述的情况不同。此外,Fz受体在神经元和胶质细胞中差异表达,提示细胞特异性模式以及因此而具有的不同生理作用。进一步的研究将有助于深入表征所描述的所有Wnt因子和受体的作用,并最终有助于设计新的治疗方法。

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