背景:大量证据表明海马是精神分裂症功能障碍的关键区域。神经影像学和其他研究表明海马功能障碍与精神病程度之间存在关系。临床数据表明,在精神病发作之前,海马多动症,并与症状严重程度相关。在这项研究中,我们试图在电子显微镜水平确定可能导致精神分裂症患者海马兴奋和抑制区域特异性失衡的电路.我们使用了精神分裂症患者和匹配对照组的前海马的死后组织。使用体视学技术,我们计数和测量突触,突触后密度(PSD),并评估了大小,三突触途径关键节点中线粒体和含小白蛋白的中间神经元的数量和光密度。与对照组相比,精神分裂症组CA3的抑制性突触数量减少,CA1的兴奋性突触数量增加;这表明抑制不足和兴奋增加。在CA1的兴奋性突触中,PSD的厚度更大,表明突触强度更大。在精神分裂症组,齿状回线粒体较少,光密度降低,功能完整性的衡量标准,在CA1。CA3中的小白蛋白中间神经元的数量和光密度较低。结果表明,兴奋电路的区域特异性增加,抑制性神经传递减少,线粒体减少或受损。这些结果与先前研究中精神分裂症海马中观察到的多动症一致。
A preponderance of evidence suggests that the hippocampus is a key region of dysfunction in schizophrenia. Neuroimaging and other studies indicate a relationship between hippocampal dysfunction and the degree of psychosis. Clinical data indicate hyperactivity in the hippocampus that precedes the onset of psychosis, and is correlated with symptom severity. In this
study, we sought to identify circuitry at the electron microscopic level that could contribute to region-specific imbalances in excitation and inhibition in the hippocampus in schizophrenia. We used postmortem tissue from the anterior hippocampus from patients with schizophrenia and matched controls. Using stereological techniques, we counted and measured synapses, postsynaptic densities (PSDs), and evaluated size, number and optical density of mitochondria and
parvalbumin-containing interneurons in key nodes of the trisynaptic pathway. Compared to controls, the schizophrenia group had decreased numbers of inhibitory synapses in CA3 and increased numbers of excitatory synapses in CA1; together, this indicates deficits in inhibition and an increase in excitation. The thickness of the PSD was larger in excitatory synapses in CA1, suggesting greater synaptic strength. In the schizophrenia group, there were fewer mitochondria in the dentate gyrus and a decrease in the optical density, a measure of functional integrity, in CA1. The number and optical density of
parvalbumin interneurons were lower in CA3. The results suggest region-specific increases in excitatory circuitry, decreases in inhibitory neurotransmission and fewer or damaged mitochondria. These results are consistent with the hyperactivity observed in the hippocampus in schizophrenia in previous studies.