Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders

被引:319
作者
Beneyto, Monica
Kristiansen, Lars V.
Oni-Orisan, Akinwunmi
McCullumsmith, Robert E.
Meador-Woodruff, James H.
机构
[1] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA
[2] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA
关键词
hippocampus; perirhinal cortex; entorhinal cortex; depression; bipolar disorder; ionotropic receptors;
D O I
10.1038/sj.npp.1301312
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1888 / 1902
页数:15
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