Kristiansen Lars V, Meador-Woodruff James H
Department of Psychiatry and The Molecular and Behavioral Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI 48109-0720, USA.
Schizophr Res. 2005 Oct 1;78(1):87-93. doi: 10.1016/j.schres.2005.06.012.
Previous studies have described abnormal expression of molecules involved in glutamatergic signaling in psychiatric illnesses, including proteins associated with receptor signaling complexes in the postsynaptic density (PSD). In particular the N-methyl-d-aspartate (NMDA) receptor complex has been associated with these illnesses. Several subcortical structures including the striatum are innervated by direct glutamatergic projections from the prefrontal cortex, and these connections may be affected in severe psychiatric illnesses. Abnormal expression of molecules critical for glutamatergic signaling in subcortical structures may thus be associated with the pathophysiology of severe psychiatric illnesses. In the present study postmortem tissue from patients with schizophrenia, bipolar disorder and major depression was used to examine striatal expression of transcripts encoding NMDA receptor interacting proteins of the PSD required for trafficking, membrane targeting and synaptic function of this receptor. We found decreased striatal expression of transcripts encoding PSD-95 and SAP-102 in bipolar disorder and of SAP-102 in major depression and schizophrenia, while no significant changes in NF--L and PSD-93 mRNAs were observed. Abnormal expression of SAP-102 in schizophrenia and SAP-102 and PSD-95 in mood disorders in subcortical structures receiving afferent glutamatergic innervation from frontal cortex suggests dysregulation of cortical-subcortical circuitry in these illnesses.
以往的研究描述了精神疾病中谷氨酸能信号传导相关分子的异常表达，包括与突触后致密区（PSD）受体信号复合物相关的蛋白质。特别是N-甲基-D-天冬氨酸（NMDA）受体复合物与这些疾病有关。包括纹状体在内的几个皮质下结构接受来自前额叶皮质的直接谷氨酸能投射支配，而这些连接在严重精神疾病中可能会受到影响。因此，皮质下结构中对谷氨酸能信号传导至关重要的分子异常表达可能与严重精神疾病的病理生理学有关。在本研究中，使用精神分裂症、双相情感障碍和重度抑郁症患者的尸检组织来检测编码NMDA受体相互作用蛋白的转录本在纹状体中的表达，这些蛋白是该受体运输、膜靶向和突触功能所需的PSD蛋白。我们发现，双相情感障碍患者中编码PSD-95和SAP-102的转录本在纹状体中的表达降低，重度抑郁症和精神分裂症患者中编码SAP-102的转录本表达降低，而NF-L和PSD-93 mRNA未观察到显著变化。在接受来自额叶皮质传入谷氨酸能神经支配的皮质下结构中，精神分裂症患者中SAP-102异常表达，情绪障碍患者中SAP-102和PSD-95异常表达，这表明这些疾病中皮质-皮质下回路失调。
