Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia
Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia
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DOI：
10.1038/npp.2016.24
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发表时间：
2016-08-01
影响因子：
7.6
通讯作者：
Lewis, David A.
中科院分区：
文献类型：
--
作者：
Enwright, John F.;Sanapala, Sowmya;Lewis, David A.
在精神分裂症患者的背外侧前额叶皮质（DLPFC）中，经常有报道称含有皮质小白蛋白（PV）的神经元发生改变，包括可检测神经元密度降低和PV水平降低。大多数PV神经元被神经元束膜网（PNNs）包围，据报道，精神分裂症患者的PNNs密度较低，这是通过紫藤凝集素（WFA）标记检测到的。然而，这些PNN改变的性质及其与PV神经元疾病相关变化的关系尚未评估。使用共聚焦显微镜，我们定量的密度和荧光强度的PV神经元和PNN标记的WFA或免疫反应的主要PNN蛋白，聚集蛋白聚糖，在DLPFC精神分裂症和匹配的比较科目。在精神分裂症中，PV细胞和PNNs的密度没有改变，但是，PV免疫反应的荧光强度在细胞体和WFA标记和聚集蛋白聚糖免疫反应在PV细胞周围的单个PNNs较低。这些研究结果表明，PV细胞和PNN的正常补体在精神分裂症中被保留，但PV蛋白和单个PNN组分的水平，特别是WFA结合的蛋白聚糖上的碳水化合物部分，较低。鉴于PV神经元在调节DLPFC微电路中的作用和PNN在调节PV细胞生理学中的作用，PV神经元及其PNN的确定的改变可能有助于精神分裂症的DLPFC功能障碍。
Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribunda agglutinin (WFA) labeling, has been reported to be lower in schizophrenia. However, the nature of these PNN alterations, and their relationship to disease-related changes in PV neurons, has not been assessed. Using confocal microscopy, we quantified the densities and fluorescence intensities of PV neurons and PNNs labeled with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects. In schizophrenia, the densities of PV cells and of PNNs were not altered; however, the fluorescence intensities of PV immunoreactivity in cell bodies and of WFA labeling and aggrecan immunoreactivity in individual PNNs around PV cells were lower. These findings indicate that the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties on proteoglycans to which WFA binds, are lower. Given the roles of PV neurons in regulating DLPFC microcircuits and of PNNs in regulating PV cellular physiology, the identified alterations in PV neurons and their PNNs could contribute to DLPFC dysfunction in schizophrenia.