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胶质细胞源性脑源性神经营养因子受体的特征:中枢和外周神经系统对损伤的不同反应

Characterization of glial trkB receptors: differential response to injury in the central and peripheral nervous systems.

作者信息

Frisén J, Verge V M, Fried K, Risling M, Persson H, Trotter J, Hökfelt T, Lindholm D

机构信息

Department of Neurochemistry, Max-Planck Institute for Psychiatry, Martinsried, Germany.

出版信息

Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4971-5. doi: 10.1073/pnas.90.11.4971.

Abstract

In situ hybridization on sections from the adult rat peripheral and central nervous systems demonstrated that trkB mRNA was expressed not only by neurons but also by cells in central nervous system white matter as well as by Schwann cells in the sciatic nerve. In situ hybridization with an oligonucleotide complementary to the trkB tyrosine kinase domain could only demonstrate mRNA in neurons, indicating expression of truncated trkB receptors lacking the tyrosine kinase domain by glial cells. RNA blot analysis was performed on separately cultured central nervous system glial cells to study which cell types express trkB mRNA. Several transcripts encoding truncated trkB receptors were expressed at high levels in O-2A progenitors, astrocytes, and oligodendrocytes, but not trkB mRNA could be detected in microglia. The expression of trkB mRNA by glial cells in vivo was also investigated after injury; strongly elevated levels of mRNA encoding truncated receptors were detected in the glial scar formed after an incision in the spinal cord dorsal funiculus. In contrast, in the cut sciatic nerve, trkB mRNA decreased distal to the transection, and by 3 weeks only very low levels of mRNA could be detected. Immunoelectron microscopy located trkB-like immunoreactivity to axons and Schwann cells in the sciatic nerve. The expression of truncated trkB receptors by astrocytes, oligodendrocytes, and Schwann cells and the altered levels in response to injury indicate that glial trkB receptors may serve an important function in the intact and injured nervous system.

摘要

对成年大鼠外周和中枢神经系统切片进行的原位杂交表明,trkB mRNA不仅由神经元表达,还由中枢神经系统白质中的细胞以及坐骨神经中的施万细胞表达。用与trkB酪氨酸激酶结构域互补的寡核苷酸进行原位杂交,只能在神经元中检测到mRNA,这表明神经胶质细胞表达缺乏酪氨酸激酶结构域的截短型trkB受体。对单独培养的中枢神经系统神经胶质细胞进行RNA印迹分析,以研究哪些细胞类型表达trkB mRNA。在少突胶质前体细胞、星形胶质细胞和少突胶质细胞中,几种编码截短型trkB受体的转录本高水平表达,但在小胶质细胞中未检测到trkB mRNA。还研究了损伤后神经胶质细胞在体内trkB mRNA的表达;在脊髓背索切开后形成的胶质瘢痕中,检测到编码截短型受体的mRNA水平显著升高。相反,在切断的坐骨神经中,trkB mRNA在横断远端减少,到3周时只能检测到非常低水平的mRNA。免疫电子显微镜将trkB样免疫反应定位于坐骨神经的轴突和施万细胞。星形胶质细胞、少突胶质细胞和施万细胞表达截短型trkB受体以及损伤后水平的改变表明,神经胶质trkB受体可能在完整和受损的神经系统中发挥重要作用。

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