Benes F M, Todtenkopf M S, Kostoulakos P
Laboratory of Structural Neuroscience, McLean Hospital, Belmont, Massachusetts 02178, USA.
Hippocampus. 2001;11(5):482-91. doi: 10.1002/hipo.1065.
Recent postmortem studies have suggested that changes in the regulation of kainate-sensitive glutamate receptors (kainate receptors) in the hippocampus may play a role in schizophrenia. To explore this possibility further, the distribution of immunoreactivity (IR) for the GluR5,6,7 subunits of the KR was assessed in a cohort consisting of 15 normal controls, 15 schizophrenics, and 9 manic depressives matched for age and postmortem interval (PMI). Cross sections of hippocampus showed abundant GluR5,6,7-IR on apical dendrites of pyramidal neurons in the stratum radiatum and stratum moleculare. In normal controls, both the numerical and length density of IR dendrites were much higher in sector CA2 than in sectors CA3 or CA1. When data for the individual groups were separately examined, the schizophrenics showed a 30-35% reduction in the density of GluR5,6,7-IR dendrites found in both stratum radiatum and stratum moleculare of sectors CA3 and CA2, as well as proximal and middle portions of CA1. In CA2, the magnitude of this decrease in schizophrenia was 2.5 times larger than that seen in any of the other sectors. For the manic depressive group, no significant differences were observed in any sectors or laminae examined. The potential confounding effects of either age, PMI, or neuroleptic exposure do not explain the reduced density of IR dendrites detected in the schizophrenic group. Taken together, the preferential reduction of GluR5,6,7-IR observed on apical dendrites of pyramidal neurons is consistent with a functional downregulation of the kainate receptor in the hippocampus of schizophrenic brain.
近期的尸检研究表明，海马体中对红藻氨酸敏感的谷氨酸受体（红藻氨酸受体）调节的变化可能在精神分裂症中起作用。为了进一步探究这种可能性，在一个由15名正常对照者、15名精神分裂症患者和9名年龄及死后间隔时间（PMI）相匹配的躁郁症患者组成的队列中，评估了红藻氨酸受体的GluR5、6、7亚基的免疫反应性（IR）分布。海马体的横断面显示，在辐射层和分子层的锥体神经元顶端树突上有丰富的GluR5、6、7-IR。在正常对照者中，CA2区IR树突的数量密度和长度密度均远高于CA3区或CA1区。当分别检查各个组的数据时，精神分裂症患者在CA3区和CA2区的辐射层和分子层以及CA1区的近端和中部发现的GluR5、6、7-IR树突密度降低了30%-35%。在CA2区，精神分裂症患者这种降低的幅度比其他任何区域都大2.5倍。对于躁郁症组，在所检查的任何区域或层中均未观察到显著差异。年龄、PMI或抗精神病药物暴露的潜在混杂效应并不能解释精神分裂症组中检测到的IR树突密度降低。综上所述，在锥体神经元顶端树突上观察到的GluR5、6、7-IR的优先减少与精神分裂症患者海马体中红藻氨酸受体的功能下调一致。
