Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients
Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients
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DOI：
10.1038/sj.mp.4000718
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发表时间：
2000-05-01
影响因子：
11
通讯作者：
Nawa, H
中科院分区：
文献类型：
--
作者：
Takahashi, M;Shirakawa, O;Nawa, H
以往的神经病理学研究表明，精神分裂症患者的皮质边缘系统表达各种突触分子的异常水平，已知这些分子受神经分化因子神经营养因子的影响。因此，我们测定了精神分裂症患者和对照受试者死后大脑中神经营养因子及其受体的水平与精神分裂症的分子损伤的关系。在所检测的神经营养因子中，脑源性神经营养因子(BDNF)的水平在精神分裂症患者的前扣带回皮质和海马区显著升高，但神经生长因子和神经营养因子-3的水平在所检测的任何区域都没有变化。同时，受BDNF影响的TrkB受体和Calbindin-D在海马区或前额叶皮质的表达显著减少。然而，抗精神病药物的治疗似乎并不能模拟神经营养的变化。患者停药或长期给予氟哌啶醇都不会改变脑源性神经营养因子的水平。这些发现表明，神经营养异常与精神分裂症患者的皮质边缘结构有关，并可能为疾病的病理表现提供分子底物。
Previous neuropathological studies have revealed that the corticolimbic system of schizophrenic patients expresses abnormal levels of various synaptic molecules, which are known to be influenced by the neuronal differentiation factors, neurotrophins. Therefore, we determined levels of neurotrophins and their receptors in the postmortem brains of schizophrenic patients and control subjects in relation to molecular impairments in schizophrenia. Among the neurotrophins examined, levels of brain-derived neurotrophic factor (BDNF) were elevated specifically in the anterior cingulate cortex and hippocampus of schizophrenic patients, but levels of nerve growth factors and neurotrophin-3 showed no change in any of the regions examined. In parallel, the expressions of TrkB receptor and calbindin-D, which are both influenced by BDNF, were reduced significantly in the hippocampus or the prefrontal cortex. However, neuroleptic treatment did not appear to mimic the neurotrophic change. Neither withdrawal of drug treatment in patients nor chronic administration of haloperidol to rats altered levels of BDNF. These findings suggest that neurotrophic abnormality is associated with the corticolimbic structures of schizophrenic patients and might provide the molecular substrate for pathological manifestations of the illness.