Co-localization of brain-derived neurotrophic factor (BDNF) and wild-type huntingtin in normal and quinolinic acid-lesioned rat brain
Co-localization of brain-derived neurotrophic factor (BDNF) and wild-type huntingtin in normal and quinolinic acid-lesioned rat brain
复制标题
DOI：
10.1046/j.1460-9568.2003.02844.x
复制
发表时间：
2003-09-01
影响因子：
3.4
通讯作者：
Bernardi, G
中科院分区：
文献类型：
--
作者：
Fusco, FR;Zuccato, C;Bernardi, G
在亨廷顿病（HD）中已经描述了亨廷顿蛋白介导的脑源性神经营养因子（BDNF）基因转录的丧失[Zuccato等人（2001）Science，293，493-498]。已经表明BDNF在大脑皮层的锥体层中合成并在纹状体中释放[Altar等（1997）Nature，389，856-860; Conner等（1997）J. Neurosci.，17，2295-2313]。在这里，我们展示了BDNF在正常大鼠脑中含有亨廷顿蛋白的神经元中的细胞定位;我们的双标记免疫荧光研究表明，亨廷顿蛋白和BDNF共包含在运动皮层的锥体神经元中的大约99%。在纹状体中，亨廷顿蛋白在75%的含有BDNF的神经元中表达。在正常纹状体中，我们还表明BDNF包含在胆碱能和含NOS的中间神经元中，它们对HD变性具有相对抗性。此外，我们发现纹状体兴奋性毒性损伤后皮质神经元的亨廷顿蛋白和BDNF免疫反应性降低。我们的数据得到证实，通过ELISA研究BDNF和蛋白质印迹分析亨廷顿蛋白在皮质的喹啉酸（QUIN）损伤的半球。在受损的纹状体，我们描述了纹状体胆碱能神经元的亚群，生存退化，含有BDNF。在正常皮质中，BDNF包含在几乎所有含有亨廷顿蛋白的神经元中，沿着纹状体注射QUIN后BDNF表达减少，这一发现表明，亨廷顿蛋白可能是皮质中BDNF产生所必需的。
Loss of huntingtin-mediated brain-derived neurotrophic factor (BDNF) gene transcription has been described in Huntington's disease (HD) [Zuccato et al. (2001) Science, 293, 493-498]. It has been shown that BDNF is synthesized in the pyramidal layer of cerebral cortex and released in the striatum [Altar et al (1997) Nature, 389, 856-860; Conner et al. (1997) J. Neurosci., 17, 2295-2313]. Here we show the cellular localization of BDNF in huntingtin-containing neurons in normal rat brain; our double-label immunofluorescence study shows that huntingtin and BDNF are co-contained in approximate to99% of pyramidal neurons of motor cortex. In the striatum, huntingtin is expressed in 75% of neurons containing BDNF In normal striatum we also show that BDNF is contained in cholinergic and in NOS-containing interneurons, which are relatively resistant to HD degeneration. Furthermore, we show a reduction in huntingtin and in BDNF immuno reactivity in cortical neurons after striatal excitotoxic lesion. Our data are confirmed by an ELISA study of BDNF and by a Western blot analysis of huntingtin in cortex of quinolic acid (QUIN)-lesioned hemispheres. In the lesioned striatum we describe that the striatal subpopulation of cholinergic neurons, surviving degeneration, contain BDNF. The finding that BDNF is contained in nearly all neurons that contain huntingtin in the normal cortex, along with the reduced expression of BDNF after QUIN injection of the striatum, shows that huntingtin may be required for BDNF production in cortex.