Weis S, Llenos I C, Dulay J R, Verma N, Sabunciyan S, Yolken R H
Laboratory of Brain Research and Neuropathology, Department of Psychiatry, Uniformed Services University of the Health Sciences, and Stanley Medical Research Institute, Bethesda, MD 20814, USA.
J Neural Transm (Vienna). 2007 Feb;114(2):261-71. doi: 10.1007/s00702-006-0544-0. Epub 2006 Aug 10.
Although, the pathogenetic mechanisms of schizophrenia, bipolar disorder, and major depression are not clearly understood, various neurotransmitter systems are reported to have altered expression patterns of their receptor and transporter proteins. Changes in the expression of the neutral amino acid transporter 1 (ASCT-1) protein in the anterior cingulate gyrus and the hippocampus were investigated using immunohistochemistry and western blotting. A significant decrease in ASCT-1 immunoreactivity in neurons in the cingulate cortex as well as astrocytes of the white matter was seen in schizophrenia. In bipolar disorder and major depression, similar results were seen for neurons. In the hippocampus, there was a striking loss of immunoreactivity on astrocytes, neurons and interneurons in multiple regions in schizophrenia and bipolar disorder, while only minor changes were seen in major depression. The altered expression of ASCT-1 in neurons and astrocytes reflects profound changes in glutamatergic neurotransmission and highlights a significant role of astrocytes in the pathophysiology of neurotransmission in these major psychiatric disorders.
尽管精神分裂症、双相情感障碍和重度抑郁症的发病机制尚不清楚，但据报道，各种神经递质系统的受体和转运蛋白表达模式发生了改变。采用免疫组织化学和蛋白质印迹法研究了前扣带回和海马中中性氨基酸转运体1（ASCT-1）蛋白的表达变化。在精神分裂症患者中，扣带回皮质神经元以及白质星形胶质细胞中的ASCT-1免疫反应性显著降低。在双相情感障碍和重度抑郁症患者中，神经元也出现了类似的结果。在海马中，精神分裂症和双相情感障碍患者多个区域的星形胶质细胞、神经元和中间神经元的免疫反应性显著丧失，而在重度抑郁症患者中仅观察到轻微变化。神经元和星形胶质细胞中ASCT-1表达的改变反映了谷氨酸能神经传递的深刻变化，并突出了星形胶质细胞在这些主要精神疾病神经传递病理生理学中的重要作用。
