Beneyto Monica, Kristiansen Lars V, Oni-Orisan Akinwunmi, McCullumsmith Robert E, Meador-Woodruff James H
Department of Psychiatry, University of Pittsburgh, 3801 O'Hara Street, Pittsburgh, PA 15213, USA.
Neuropsychopharmacology. 2007 Sep;32(9):1888-902. doi: 10.1038/sj.npp.1301312. Epub 2007 Feb 14.
Pharmacological and anatomical evidence suggests that abnormal glutamate neurotransmission may be associated with the pathophysiology of schizophrenia and mood disorders. Medial temporal lobe structural alterations have been implicated in schizophrenia and to a lesser extent in mood disorders. To comprehensively examine the ionotropic glutamate receptors in these illnesses, we used in situ hybridization to determine transcript expression of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and kainate receptor subunits in the medial temporal lobe of subjects with schizophrenia, bipolar disorder (BD), or major depression (MDD). We used receptor autoradiography to assess changes in glutamate receptor binding in the same subjects. Our results indicate that there are region- and disorder-specific abnormalities in the expression of ionotropic glutamate receptor subunits in schizophrenia and mood disorders. We did not find any changes in transcript expression in the hippocampus. In the entorhinal cortex, most changes in glutamate receptor expression were associated with BD, with decreased GluR2, GluR3, and GluR6 mRNA expression. In the perirhinal cortex we detected decreased expression of GluR5 in all three diagnoses, of GluR1, GluR3, NR2B in both BD and MDD, and decreased NR1 and NR2A in BD and MDD, respectively. Receptor binding showed NMDA receptor subsites particularly affected in the hippocampus, where MK801 binding was reduced in schizophrenia and BD, and MDL105,519 and CGP39653 binding were increased in BD and MDD, respectively. In the hippocampus AMPA and kainate binding were not changed. We found no changes in the entorhinal and perirhinal cortices. These data suggest that glutamate receptor expression is altered in the medial temporal lobe in schizophrenia and the mood disorders. We propose that disturbances in glutamate-mediated synaptic transmission in the medial temporal lobe are important factors in the pathophysiology of these severe psychiatric illnesses.
药理学和解剖学证据表明，谷氨酸神经传递异常可能与精神分裂症和情绪障碍的病理生理学有关。内侧颞叶结构改变与精神分裂症有关，在情绪障碍中程度较轻。为了全面研究这些疾病中的离子型谷氨酸受体，我们采用原位杂交技术来确定精神分裂症、双相情感障碍（BD）或重度抑郁症（MDD）患者内侧颞叶中N-甲基-D-天冬氨酸（NMDA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和海人酸受体亚基的转录本表达。我们使用受体放射自显影术来评估同一受试者中谷氨酸受体结合的变化。我们的结果表明，精神分裂症和情绪障碍中离子型谷氨酸受体亚基的表达存在区域和疾病特异性异常。我们在海马体中未发现转录本表达有任何变化。在内嗅皮质中，谷氨酸受体表达的大多数变化与BD有关，GluR2、GluR3和GluR6 mRNA表达降低。在嗅周皮质中，我们在所有三种诊断中均检测到GluR5表达降低，在BD和MDD中均检测到GluR1、GluR3、NR2B表达降低，在BD和MDD中分别检测到NR1和NR2A表达降低。受体结合显示NMDA受体亚位点在海马体中受到特别影响，其中MK801结合在精神分裂症和BD中降低，MDL105,519和CGP39653结合在BD和MDD中分别增加。在海马体中，AMPA和海人酸结合未发生变化。我们在内嗅皮质和嗅周皮质中未发现变化。这些数据表明，精神分裂症和情绪障碍患者的内侧颞叶中谷氨酸受体表达发生了改变。我们认为，内侧颞叶中谷氨酸介导的突触传递紊乱是这些严重精神疾病病理生理学中的重要因素。
