Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients
Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients
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DOI：
10.1186/s40345-019-0161-0
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发表时间：
2019-12-01
影响因子：
4
通讯作者：
Nacher, Juan
中科院分区：
文献类型：
--
作者：
Alcaide, Julia;Guirado, Ramon;Nacher, Juan
前额叶皮层（PFC）中间神经元的结构和生理改变是不同精神疾病病因的重要因素。在神经元间亚群中，表达小白蛋白（PV）的细胞似乎特别受影响。有趣的是，在发育和成年期间，这些中间神经元的连接受到神经元周围网络（PNNs）的调节，PNNs是细胞外基质的特殊区域，通常围绕着表达PV的神经元。先前的报告发现精神分裂症患者PFC中pnn的密度异常。然而，尽管一些研究描述了双相情感障碍患者某些皮质外区域PNNs的改变，但尚无关于双相情感障碍或重度抑郁症患者前额皮质PNNs的研究。因此，我们分析了斯坦利神经病理学协会（Stanley Neuropathology Consortium）提供的背外侧PFC （DLPFC）尸检切片中pnn的密度，其中包括对照组、精神分裂症、双相情感障碍和重度抑郁症患者。结果PV+细胞和pnn的分布无明显差异，pnn包围的PV+中间神经元的比例也无明显差异。各实验组PV+中间神经元密度相似，但双相情感障碍患者DLPFC中pnn密度明显降低，精神分裂症患者pnn密度有降低的趋势。在评估被pnn包围的PV+细胞密度时，没有发现差异。有趣的是，在评估人口统计数据的影响时，我们发现pnn的密度与精神病的存在呈负相关。结论本研究结果表明前额皮质PNNs及其在神经元可塑性调节中的作用可能在双相情感障碍和精神分裂症的病因病理学中起作用。我们的研究结果还表明，这些细胞外基质的特殊区域与精神病的存在之间存在联系。
Background Alterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders. Among the interneuronal subpopulations, parvalbumin (PV) expressing cells appear to be specially affected. Interestingly, during development and adulthood the connectivity of these interneurons is regulated by the presence of perineuronal nets (PNNs), specialized regions of the extracellular matrix, which are frequently surrounding PV expressing neurons. Previous reports have found anomalies in the density of PNNs in the PFC of schizophrenic patients. However, although some studies have described alterations in PNNs in some extracortical regions of bipolar disorder patients, there are no studies focusing on the prefrontocortical PNNs of bipolar or major depression patients. For this reason, we have analyzed the density of PNNs in post-mortem sections of the dorsolateral PFC (DLPFC) from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients. Results We have not observed differences in the distribution of PV+ cells or PNNs, or in the percentage of PV+ interneurons surrounded by PNNs. The density of PV+ interneurons was similar in all the experimental groups, but there was a significantly lower density of PNNs in the DLPFC of bipolar disorder patients and a tendency towards a decrease in schizophrenic patients. No differences were found when evaluating the density of PV+ cells surrounded by PNNs. Interestingly, when assessing the influence of demographic data, we found an inverse correlation between the density of PNNs and the presence of psychosis. Conclusions The present results point to prefrontocortical PNNs and their role in the regulation of neuronal plasticity as putative players in the etiopathology of bipolar disorder and schizophrenia. Our findings also suggest a link between these specialized regions of the extracellular matrix and the presence of psychosis.