IN-SITU HYBRIDIZATION OF TRKB AND TRKC RECEPTOR MESSENGER-RNA IN RAT FOREBRAIN AND ASSOCIATION WITH HIGH-AFFINITY BINDING OF [I-125] BDNF, [I-125] NT-4/5 AND [I-125] NT-3
IN-SITU HYBRIDIZATION OF TRKB AND TRKC RECEPTOR MESSENGER-RNA IN RAT FOREBRAIN AND ASSOCIATION WITH HIGH-AFFINITY BINDING OF [I-125] BDNF, [I-125] NT-4/5 AND [I-125] NT-3
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DOI：
10.1111/j.1460-9568.1994.tb01001.x
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发表时间：
1994-09-01
影响因子：
3.4
通讯作者：
WIEGAND, SJ
中科院分区：
文献类型：
--
作者：
ALTAR, CA;SIUCIAK, JA;WIEGAND, SJ
TrkB和TrkC受体酪氨酸激酶已被鉴定为神经营养因子脑源性神经营养因子（BDNF）和神经营养因子4/5 （NT-4/5）和NT-3的高亲和受体。通过与trkB和trkC mRNA的细胞内（酪氨酸激酶）或细胞外（配体结合）区域互补的反义核糖探针的原位杂交，以及高亲和力[I-125]BDNF、[I-125]NT-4/5和[I-125]NT-3结合位点在邻近大鼠脑区域的分布，鉴定和绘制了这些受体类别。两种方法均表明TrkB和TrkC受体丰富且在整个大脑中广泛表达。激酶或细胞外结构域trkC探针几乎在前脑的每个主要区域以质量相似的方式标记神经元体。除了脑动脉和小动脉内的元素外，trkC探针都没有标记非神经元细胞。激酶结构域trkB探针只与神经元杂交。表达trkB的神经元比表达trkC的神经元分布更广泛。胞外结构域trkB探针标记的神经元与trkB激酶结构域探针的相对分布相同，但也与非神经细胞，特别是星形胶质细胞、室管膜和脉络膜上皮细胞广泛杂交。[I-125]NT-3结合位点的分布与trkC杂交的分布大体相似，特别是在新皮层、纹状体和丘脑。[I-125]BDNF和[I-125]NT-4/5的结合位点比[I-125]NT-3的结合位点分布更广、密度更大，且与trkB杂交模式相似。这些模式与脑内TrkC受体被[I-125]NT-3优先结合，TrkB受体被[I-125]BDNF和[I-125]NT-4/5优先结合一致。用激酶和细胞外结构域探针获得的trkC杂交的主要神经元模式在质量上无法区分，这表明截断和全长形式的trkC在广泛重叠的神经元群体中表达。与TrkC形成鲜明对比的是，全长和截断形式的TrkB的表达似乎在很大程度上是分离的，主要分别在神经元和非神经元细胞上表达。TrkB和TrkC的全长、信号转导形式在神经元中的丰富和广泛分布预示着它们的同源配体BDNF、NT-4/5和NT-3可能对成熟脑内的大部分神经元起直接作用。
The TrkB and TrkC receptor tyrosine kinases have been identified as high-affinity receptors for the neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) and NT-3 respectively. These receptor classes were identified and mapped by the in situ hybridization of antisense riboprobes complementary to portions of the intracellular (tyrosine kinase) or extracellular (ligand-binding) domains of trkB and trkC mRNA, and by the distribution of high-affinity [I-125]BDNF, [I-125]NT-4/5 and [I-125]NT-3 binding sites in adjacent rat brain sections. Both methods showed that TrkB and TrkC receptors are abundant and widely expressed throughout the brain. Kinase or extracellular domain trkC probes labelled neuronal somata in a qualitatively similar manner in virtually every major area of the forebrain. Neither trkC probe labelled non-neuronal cells except for elements within cerebral arteries and arterioles. The kinase domain trkB probe hybridized exclusively to neurons. Neurons expressing trkB were even more widely distributed than those expressing trkC. The extracellular domain trkB probe labelled neurons with the same relative distribution as the trkB kinase domain probe, but also hybridized extensively with non-neural cells, particularly astrocytes, ependyma and choroid epithelium cells. The distribution of [I-125]NT-3 binding sites generally resembled that of trkC hybridization, particularly in the neocortex, striatum and thalamus. [I-125]BDNF and [I-125]NT-4/5 binding sites were more widely distributed and denser than those for [I-125]NT-3, and resembled the trkB hybridization pattern. These patterns are consistent with the preferential binding in the brain of TrkC receptors by [I-125]NT-3 and of TrkB receptors by [I-125]BDNF and [I-125]NT-4/5. That the predominantly neuronal patterns of hybridization obtained with kinase and extracellular domain probes for trkC are qualitatively indistinguishable suggests that truncated and full-length forms of TrkC are expressed within extensively overlapping populations of neurons. In marked contrast to TrkC, expression of the full-length and truncated forms of TrkB appears to be largely segregated, being expressed principally on neurons and non-neuronal cells respectively. The abundant and widespread neuronal distribution of full-length, signal-transducing forms of TrkB and TrkC predict that their cognate ligands, BDNF, NT-4/5 and NT-3, may exert direct effects on a large proportion of neurons within the mature brain.