Neurotrophin receptor activation and expression in human postmortem brain: effect of suicide.
Neurotrophin receptor activation and expression in human postmortem brain: effect of suicide.
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DOI：
10.1016/j.biopsych.2008.08.035
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发表时间：
2009-02-15
影响因子：
10.6
通讯作者：
Pandey, Ghanshyam N.
中科院分区：
文献类型：
--
作者：
Dwivedi, Yogesh;Rizavi, Hooriyah S.;Zhang, Hui;Mondal, Amal C.;Roberts, Rosalinda C.;Conley, Robert R.;Pandey, Ghanshyam N.
神经营养蛋白的生理功能通过与两种不同受体结合而发生：pan 75神经营养蛋白受体（p75 NTR）和原溶素受体激酶家族（Trks A、B和C）。最近，我们报道了神经营养因子和TrkB的表达在自杀受试者的大脑中减少。目前的研究检查是否表达和激活的Trk受体和表达的p75 NTR的改变，在这些科目的大脑。采用定量RT-PCR和Western blot检测自杀组和正常对照组前额叶皮层（PFC）和海马TrkA、B、C和p75 NTR的表达水平。通过免疫沉淀法测定Trks的活化，然后使用磷酸酪氨酸抗体进行Western印迹。在海马，较低的TrkA和TrkC的mRNA水平，观察自杀受试者。PFC中TrkA的mRNA水平降低，TrkC的mRNA水平无明显变化。另一方面，PFC和海马中p75 NTR的mRNA水平增加。免疫标记研究显示与mRNA观察到的结果相似。此外，海马中所有Trks的磷酸化均降低，但在PFC中，仅观察到TrkA和B的磷酸化降低。自杀组PFC和海马中p75 NTR与Trks的表达比例也增加。我们的研究结果表明，不仅减少功能的Trks在自杀受试者的大脑中，但增加的比例p75 NTR的Trks表明可能激活的途径是凋亡的性质。这些发现在自杀的病理生理学中可能是至关重要的。
The physiological functions of neurotrophins occur through binding to two different receptors: pan75 neurotrophin receptor (p75NTR) and a family of tropomysin receptor kinases (Trks A, B, and C). Recently, we reported that expression of neurotrophins and TrkB were reduced in brains of suicide subjects. Present study examines whether expression and activation of Trk receptors and expression of p75NTR are altered in brain of these subjects. Expression levels of TrkA, B, C, and of p75NTR were measured by quantitative RT-PCR and Western blot in prefrontal cortex (PFC) and hippocampus of suicide and normal control subjects. The activation of Trks was determined by immunoprecipitation followed by Western blotting using phosphotyrosine antibody. In hippocampus, lower mRNA levels of TrkA and TrkC were observed in suicide subjects. In the PFC, the mRNA level of TrkA was decreased, without any change in TrkC. On the other hand, the mRNA level of p75NTR was increased in both PFC and hippocampus. Immunolabeling studies showed similar results as observed for the mRNAs. In addition, phosphorylation of all Trks was decreased in hippocampus, but in PFC, decreased phosphorylation was noted only for TrkA and B. Increased expression ratios of p75NTR to Trks were also observed in PFC and hippocampus of suicide subjects. Our results suggest not only reduced functioning of Trks in brains of suicide subjects but that increased ratios of p75NTR to Trks indicate possible activation of pathways that are apoptotic in nature. These findings may be crucial in the pathophysiology of suicide.
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DOI：
10.1002/neu.480251107
发表时间：
1994-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
BARBACID, M
通讯作者：
BARBACID, M
影响因子：
3.4
作者：
BARBANY, G;PERSSON, H
通讯作者：
PERSSON, H
影响因子：
11
作者：
Dwivedi, Y;Rizavi, HS;Pandey, GN
通讯作者：
Pandey, GN
影响因子：
3.3
作者：
CLARY, DO;WESKAMP, G;REICHARDT, LF
通讯作者：
REICHARDT, LF
影响因子：
4.7
作者：
Bilderback, TR;Gazula, VR;Dobrowsky, RT
通讯作者：
Dobrowsky, RT