Oligodendrocyte and Interneuron Density in Hippocampal Subfields in Schizophrenia and Association of Oligodendrocyte Number with Cognitive Deficits
Oligodendrocyte and Interneuron Density in Hippocampal Subfields in Schizophrenia and Association of Oligodendrocyte Number with Cognitive Deficits
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DOI：
10.3389/fncel.2010.00078
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发表时间：
2016-03-30
影响因子：
5.3
通讯作者：
Schmitt, Andrea
中科院分区：
文献类型：
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作者：
Falkai, Peter;Steiner, Johann;Schmitt, Andrea
在精神分裂症中，先前对前海马、后海马和总海马亚区的体视学尸检显示总神经元数量没有变化，但确实显示 CA4 中少突胶质细胞数量减少，该区域对应于齿状回 (DG) 的多形层。然而，这些研究仅根据尼氏染色的形态学标准鉴定了少突胶质细胞，并且没有使用免疫组织化学标记物评估中间神经元的改变。此外，海马后部的发现与认知缺陷之间的关系仍然未知。根据现有的临床记录，我们对患有明确的和可能的认知功能障碍的患者进行了比较； 9 名患者的记录中有明确的（n = 4）或可能的（n = 5）认知功能障碍的证据。此外，我们评估了少突胶质细胞转录因子 Olig1 和 Olig2 免疫染色的两个少突胶质细胞亚群的密度以及小白蛋白免疫标记的中间神经元的密度。我们研究了我们在之前发表的体视学研究中检查的同一精神分裂症患者（SZ；n = 10）和健康对照（n = 10）的死后大脑中的后海马亚区域。我们的体视学研究发现，患有明确认知缺陷的患者左下托（p = 0.014）和右（p = 0.050）CA4、左CA2/3（p = 0.050）、左CA1（p = 0.027）以及左（p = 0.050）和右（p = 0.014）下托的总/尼氏染色少突胶质细胞数量减少。与可能存在认知缺陷的患者的海马前部相比。在本研究中，我们发现海马后部的明确认知缺陷没有显着影响，而在整个海马 SZ 中，有明确认知缺陷的左侧 (p = 0.050) 和右侧 (p = 0.050) DG 和左侧 CA2/3 (p = 0.050) 少突胶质细胞数量减少。我们没有发现 SZ 和对照组后海马任何亚区域的 Olig1、Olig2 或小清蛋白阳性细胞密度存在显着差异。根据我们的体视学研究结果，我们假设精神分裂症患者前海马和整个海马中少突胶质细胞数量的减少可能通过损害该结构的连通性而导致认知缺陷。在后海马体中，我们无法复制之前报道的整个海马体中间神经元减少的发现。
In schizophrenia, previous stereological post-mortem investigations of anterior, posterior, and total hippocampal subfields showed no alterations in total neuron number but did show decreased oligodendrocyte numbers in CA4, an area that corresponds to the polymorph layer of the dentate gyrus (DG). However, these investigations identified oligodendrocytes only on the basis of morphological criteria in Nissl staining and did not assess alterations of interneurons with immunohistochemical markers. Moreover, the association of findings in the posterior hippocampus with cognitive deficits remains unknown. On the basis of the available clinical records, we compared patients with definite and possible cognitive dysfunction; nine patients had evidence in their records of either definite (n = 4) or possible (n = 5) cognitive dysfunction. Additionally, we assessed the density of two oligodendrocyte subpopulations immunostained by the oligodendrocyte transcription factors Olig1 and Olig2 and of interneurons immunolabeled by parvalbumin. We investigated posterior hippocampal subregions in the post-mortem brains of the same schizophrenia patients (SZ; n = 10) and healthy controls (n = 10) we examined in our previously published stereological studies. Our stereological studies found that patients with definite cognitive deficits had decreased total/Nissl-stained oligodendrocyte numbers in the left (p = 0.014) and right (p = 0.050) CA4, left CA2/3 (p = 0.050), left CA1 (p = 0.027), and left (p = 0.050) and right (p = 0.014) subiculum of the anterior part of the hippocampus compared to patients with possible cognitive deficits. In the present study, we found no significant influence of definite cognitive deficits in the posterior part of the hippocampus, whereas in the entire hippocampus SZ with definite cognitive deficits showed decreased oligodendrocyte numbers in the left (p = 0.050) and right (p = 0.050) DG and left CA2/3 (p = 0.050). We did not find significant differences in Olig1-, Olig2-, or parvalbumin-positive cell density between SZ and controls in any of the subregions of the posterior hippocampus. Based on the results from our stereological study we hypothesize that a decreased number of oligodendrocytes in the anterior and entire hippocampus may be involved in cognitive deficits by impairing the connectivity of this structure in schizophrenia. In the posterior hippocampus, we could not replicate previously reported findings of decreased interneurons from the entire hippocampus.