Roberts Rosalinda C, McCollum Lesley A, Schoonover Kirsten E, Mabry Samuel J, Roche Joy K, Lahti Adrienne C
Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham, AL 35294, United States of America.
Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham, AL 35294, United States of America.
Schizophr Res. 2022 Nov;249:4-15. doi: 10.1016/j.schres.2020.01.016. Epub 2020 Feb 1.
The aim of this paper is to summarize ultrastructural evidence for glutamatergic dysregulation in several linked regions in postmortem schizophrenia brain. Following a brief summary of glutamate circuitry and how synapses are identified at the electron microscopic (EM) level, we will review EM pathology in the cortex and basal ganglia. We will include the effects of antipsychotic drugs and the relation of treatment response. We will discuss how these findings support or confirm other postmortem findings as well as imaging results. Briefly, synaptic and mitochondrial density in anterior cingulate cortex was decreased in schizophrenia, versus normal controls (NCs), in a selective layer specific pattern. In dorsal striatum, increases in excitatory synaptic density were detected in caudate matrix, a compartment associated with cognitive and motor function, and in the putamen patches, a region associated with limbic function and in the core of the nucleus accumbens. Patients who were treatment resistant or untreated had significantly elevated numbers of excitatory synapses in limbic striatal areas in comparison to NCs and responders. Protein levels of vGLUT2, found in subcortical glutamatergic neurons, were increased in the nucleus accumbens in schizophrenia. At the EM level, schizophrenia subjects had an increase in density of excitatory synapses in several areas of the basal ganglia. In the substantia nigra, the protein levels of vGLUT2 were elevated in untreated patients compared to NCs. The density of inhibitory synapses was decreased in schizophrenia versus NCs. In schizophrenia, glutamatergic synapses are differentially affected depending on the brain region, treatment status, and treatment response.
本文旨在总结死后精神分裂症大脑中几个相关区域谷氨酸能调节异常的超微结构证据。在简要概述谷氨酸能神经回路以及如何在电子显微镜（EM）水平识别突触之后，我们将回顾皮质和基底神经节的EM病理学。我们将包括抗精神病药物的作用以及治疗反应的关系。我们将讨论这些发现如何支持或证实其他死后研究结果以及影像学结果。简而言之，与正常对照组（NCs）相比，精神分裂症患者前扣带回皮质的突触和线粒体密度以选择性层特异性模式降低。在背侧纹状体中，在与认知和运动功能相关的尾状核基质、与边缘功能相关的壳核斑块以及伏隔核核心中检测到兴奋性突触密度增加。与NCs和有反应者相比，治疗抵抗或未治疗的患者边缘纹状体区域的兴奋性突触数量显著增加。在精神分裂症患者的伏隔核中，发现于皮质下谷氨酸能神经元中的vGLUT2蛋白水平升高。在EM水平上，精神分裂症患者基底神经节几个区域的兴奋性突触密度增加。在黑质中，与NCs相比，未治疗患者的vGLUT2蛋白水平升高。与NCs相比，精神分裂症患者的抑制性突触密度降低。在精神分裂症中，谷氨酸能突触根据脑区、治疗状态和治疗反应而受到不同影响。
