Weickert C S, Ligons D L, Romanczyk T, Ungaro G, Hyde T M, Herman M M, Weinberger D R, Kleinman J E
Clinical Brain Disorders Branch, National Institute of Mental Health, Division of Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA.
Mol Psychiatry. 2005 Jul;10(7):637-50. doi: 10.1038/sj.mp.4001678.
Patients with schizophrenia have reduced neurotrophin levels in their dorsolateral prefrontal cortex (DLPFC) compared to normal unaffected individuals. The tyrosine kinase-containing receptors, trkB and trkC, mediate the growth-promoting effects of neurotrophins and respond to changes in growth factor availability. We hypothesized that trkB and/or trkC expression would be altered in the DLPFC of patients with schizophrenia. We measured mRNA encoding the tyrosine kinase domain (TK+)-containing form of trkB and measured pan trkC mRNA in schizophrenics (N=14) and controls (N=15) using in situ hybridization. TrkB and trkC mRNAs were detected in large and small neurons in multiple cortical layers of the human DLPFC. We found significantly diminished expression of trkB(TK+) mRNA in large neurons in multiple cortical layers of patients as compared to controls, while small neurons also showed reductions in trkB(TK+) mRNA that did not reach statistical significance. In normals, strong positive correlations were found between trkB(TK+) mRNA levels and brain-derived neurotrophic factor (BDNF) mRNA levels among various neurons, while no correlation between BDNF and trkB(TK+) was found in patients with schizophrenia. TrkC mRNA was also reduced in the DLPFC of schizophrenics in large neurons in layers II, III, V and VI and in small neurons in layer IV. Since neurons in the DLPFC integrate and communicate signals to various cortical and subcortical regions, these reductions in growth factor receptors may compromise the function and plasticity of the DLPFC in schizophrenia.
与正常未患病个体相比，精神分裂症患者背外侧前额叶皮质（DLPFC）中的神经营养因子水平降低。含酪氨酸激酶的受体trkB和trkC介导神经营养因子的促生长作用，并对生长因子可用性的变化做出反应。我们假设精神分裂症患者DLPFC中trkB和/或trkC的表达会发生改变。我们使用原位杂交技术，测量了精神分裂症患者（N = 14）和对照组（N = 15）中编码trkB含酪氨酸激酶结构域（TK +）形式的mRNA以及总trkC mRNA。在人类DLPFC的多个皮质层的大、小神经元中检测到了TrkB和trkC mRNA。我们发现，与对照组相比，患者多个皮质层大神经元中trkB（TK +）mRNA的表达显著降低，而小神经元中trkB（TK +）mRNA也有所降低，但未达到统计学意义。在正常人中，不同神经元之间trkB（TK +）mRNA水平与脑源性神经营养因子（BDNF）mRNA水平之间存在强正相关，而在精神分裂症患者中未发现BDNF与trkB（TK +）之间存在相关性。精神分裂症患者DLPFC中，II、III、V和VI层的大神经元以及IV层的小神经元中TrkC mRNA也减少。由于DLPFC中的神经元整合并向各种皮质和皮质下区域传递信号，这些生长因子受体的减少可能会损害精神分裂症患者DLPFC的功能和可塑性。
