Meador-Woodruff J H, Davis K L, Haroutunian V
Mental Health Research Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109-0720, USA.
Neuropsychopharmacology. 2001 May;24(5):545-52. doi: 10.1016/S0893-133X(00)00189-5.
Abnormalities of molecules associated with the glutamate synapse have been implicated in the pathophysiology of schizophrenia. Of the many glutamate receptors, those most commonly suggested to be involved in schizophrenia are the ionotropic subtypes, the NMDA, AMPA, and kainate receptors. Both the NMDA and AMPA subtypes have been extensively studied in postmortem brains of individuals with schizophrenia, but relatively little is known about the expression of the kainate subtype of glutamate receptor. In this study, we have determined cortical and striatal kainate receptor expression in brains from persons with schizophrenia and a comparison group, using both in situ hybridization and receptor autoradiography. At the level of subunit mRNA expression, a shift in subunit stoichiometry was evident in multiple regions of the prefrontal cortex, with increased expression of gluR7 mRNA and decreased expression of KA2 mRNA. Decreased kainate receptor binding was also observed in the subjects with schizophrenia, but was restricted to infragranular laminae of the prefrontal cortex. No differences in kainate receptor binding or subunit mRNA levels were found in striatum or occipital cortex, suggesting that these findings may be restricted to association cortex. These data add to the growing literature implicating ionotropic glutamate receptor disturbances in schizophrenia, and indicate that in addition to AMPA and NMDA receptors, the kainate receptors are also abnormally expressed in this illness.
与谷氨酸突触相关的分子异常已被认为与精神分裂症的病理生理学有关。在众多谷氨酸受体中，最常被认为与精神分裂症有关的是离子型亚型，即NMDA、AMPA和海人藻酸受体。NMDA和AMPA亚型在精神分裂症患者的死后大脑中都得到了广泛研究，但对于谷氨酸受体海人藻酸亚型的表达了解相对较少。在本研究中，我们使用原位杂交和受体放射自显影技术，测定了精神分裂症患者及对照组大脑皮质和纹状体中海人藻酸受体的表达。在亚基mRNA表达水平上，前额叶皮质的多个区域明显出现亚基化学计量的变化，其中gluR7 mRNA表达增加，KA2 mRNA表达减少。在精神分裂症患者中还观察到海人藻酸受体结合减少，但仅限于前额叶皮质的颗粒下层。在纹状体或枕叶皮质中未发现海人藻酸受体结合或亚基mRNA水平的差异，这表明这些发现可能仅限于联合皮质。这些数据进一步丰富了有关离子型谷氨酸受体紊乱与精神分裂症相关的文献，并表明除了AMPA和NMDA受体外，海人藻酸受体在这种疾病中也存在异常表达。
