Fenner Mark E, Achim Cristian L, Fenner Barbara Murray
, Forty Fort, PA, 18704, USA.
J Mol Histol. 2014 Jun;45(3):349-61. doi: 10.1007/s10735-013-9562-z. Epub 2013 Dec 29.
Brain derived neurotrophic factor (BDNF) is a potent mediator of cell survival and differentiation and can reverse neuronal injury associated with Parkinson's disease (PD). Tropomyosin receptor kinase B (trkB) is the high affinity receptor for BDNF. There are two major trkB isoforms, the full-length receptor (trkB.tk(+)) and the truncated receptor (trkB.t1), that mediate the diverse, region specific functions of BDNF. Both trkB isoforms are widely distributed throughout the brain, but the isoform specific distribution of trkB.t1 and trkB.tk(+) to human neurons is not well characterized. Therefore, we report the regional and neuronal distribution of trkB.tk(+) and trkB.t1 in the striatum and substantia nigra pars compacta (SNpc) of human autopsy tissues from control and PD cases. In both PD and control tissues, we found abundant, punctate distribution of trkB.tk(+) and trkB.t1 proteins in striatum and SNpc neurons. In PD, trkB.tk(+) is decreased in striatal neurites, increased in striatal somata, decreased in SNpc somata and dendrites, and increased in SNpc axons. TrkB.t1 is increased in striatal somata, decreased in striatal axons, and increased in SNpc distal dendrites. We believe changes in trkB isoform distribution and expression levels may be markers of pathology and affect the neuronal response to BDNF.
脑源性神经营养因子（BDNF）是细胞存活和分化的有效介质，可逆转与帕金森病（PD）相关的神经元损伤。原肌球蛋白受体激酶B（trkB）是BDNF的高亲和力受体。有两种主要的trkB亚型，即全长受体（trkB.tk(+)）和截短受体（trkB.t1），它们介导BDNF的多种区域特异性功能。两种trkB亚型均广泛分布于整个大脑，但trkB.t1和trkB.tk(+)在人类神经元中的亚型特异性分布尚未得到充分表征。因此，我们报告了trkB.tk(+)和trkB.t1在对照和PD病例的人类尸检组织纹状体和黑质致密部（SNpc）中的区域和神经元分布。在PD和对照组织中，我们发现trkB.tk(+)和trkB.t1蛋白在纹状体和SNpc神经元中呈丰富的点状分布。在PD中，trkB.tk(+)在纹状体神经突中减少，在纹状体胞体中增加，在SNpc胞体和树突中减少，在SNpc轴突中增加。TrkB.t1在纹状体胞体中增加，在纹状体轴突中减少，在SNpc远端树突中增加。我们认为trkB亚型分布和表达水平的变化可能是病理学标志物，并影响神经元对BDNF的反应。
