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出生后大鼠脑中表达信号转导和转录激活因子3(STAT3)的细胞的特征分析。

Characterization of STAT3-expressing cells in the postnatal rat brain.

作者信息

Gautron Laurent, De Smedt-Peyrusse Véronique, Layé Sophie

机构信息

Laboratoire de Neurobiologie Intégrative, INRA 1244-CNRS FRE 2723, Institut François Magendie, Rue Camille St Saëns, 33077 Bordeaux Cedex, France.

出版信息

Brain Res. 2006 Jul 7;1098(1):26-32. doi: 10.1016/j.brainres.2006.04.115. Epub 2006 Jun 9.

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor abundantly expressed in the postnatal brain that is involved in the differentiation of cultured astrocytes. Thus far, the cellular identity and anatomical distribution of STAT3-expressing cells in the postnatal brain is poorly known. This study identifies the cell type(s), anatomical location, and temporal distribution of STAT3-expressing cells by using immunohistochemistry and confocal microscopy on postnatal day 3 (P3), 10 (P10), and 21 (P21) rat brain sections. Furthermore, the phosphorylation of STAT3 on tyrosine and serine residues was analyzed at these different stages by immunoprecipitation followed by Western blot. STAT3 immunoreactivity was observed in the cytoplasm and nucleus of many maturating astrocytes positive for nestin (at P3) or positive for GFAP (at P10) distributed throughout the white and grey matter. Moreover, robust nuclear immunoreactivity was observed in brainstem motoneurons. Phosphorylation on tyrosine and serine was observed at P3 and increased at P10, which suggests an augmented activation of STAT3 at the mid-postnatal period. At P21, STAT3 immunoreactivity dramatically decreased to remain visible only in the cytoplasm of white matter astrocytes and hypothalamic and brainstem neuronal groups. Furthermore, while the phosphorylation of tyrosine residues tended to decrease, that of serine residues further increased. In summary, our study reveals a complex regulation of STAT3 phosphorylation in the postnatal brain and provides in vivo evidence of the specific expression of STAT3 in maturating astrocytes and brainstem motoneurons.

摘要

信号转导与转录激活因子3(STAT3)是一种在出生后脑内大量表达的转录因子,参与培养的星形胶质细胞的分化。迄今为止,出生后脑内表达STAT3的细胞的细胞身份和解剖分布尚不清楚。本研究通过对出生后第3天(P3)、第10天(P10)和第21天(P21)的大鼠脑切片进行免疫组织化学和共聚焦显微镜检查,确定了表达STAT3的细胞类型、解剖位置和时间分布。此外,通过免疫沉淀后进行蛋白质印迹分析,在这些不同阶段分析了STAT3酪氨酸和丝氨酸残基的磷酸化情况。在整个白质和灰质中分布的许多对巢蛋白呈阳性(在P3)或对胶质纤维酸性蛋白呈阳性(在P10)的成熟星形胶质细胞的细胞质和细胞核中观察到STAT3免疫反应性。此外,在脑干运动神经元中观察到强烈的核免疫反应性。在P3观察到酪氨酸和丝氨酸的磷酸化,在P10增加,这表明在出生后中期STAT3的激活增强。在P21,STAT3免疫反应性显著降低,仅在白质星形胶质细胞以及下丘脑和脑干神经元群的细胞质中仍可见。此外,虽然酪氨酸残基的磷酸化趋于减少,但丝氨酸残基的磷酸化进一步增加。总之,我们的研究揭示了出生后脑内STAT3磷酸化的复杂调节,并提供了STAT3在成熟星形胶质细胞和脑干运动神经元中特异性表达的体内证据。

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