Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala.
Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala.
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DOI：
10.1038/tp.2014.128
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发表时间：
2015-01-20
影响因子：
6.8
通讯作者：
Berretta S
中科院分区：
文献类型：
--
作者：
Pantazopoulos H;Markota M;Jaquet F;Ghosh D;Wallin A;Santos A;Caterson B;Berretta S
神经周围网络（PNNs）是一种特殊的细胞外基质聚集体，围绕着不同的神经元群，调节突触功能和可塑性。先前的研究结果显示，精神分裂症（SZ）患者的杏仁核、内嗅皮层和前额叶皮层的PNN明显减少，但双相情感障碍（BD）患者的PNN明显减少。这些研究是使用硫酸软骨素蛋白聚糖（CSPG）凝集素标记物进行的。在这里，我们验证了CSPG聚集蛋白和聚集蛋白中高度代表的6-硫酸软骨素（CS-6）链可能导致这些异常的假设。在健康对照、SZ和BD受试者的杏仁核中使用了抗聚集蛋白和CS-6的抗体（3B3和CS56）。在对照组中，聚集体免疫反应性（IR）在pnn和胶质细胞中被观察到。抗体3B3，而非CS56，也标记了杏仁核中的PNNs。此外，CS56和3B3 IR密集簇分别包裹CS56-和3B3-IR胶质细胞。在SZ中，聚集蛋白-和3B3- ir pnn的数量减少，聚集蛋白- ir胶质细胞和CS-6 (3B3和CS56)- ir“簇”的数量也明显减少。在BD中，3B3-IR pnn和CS56-IR簇的数量减少。我们的研究结果显示，SZ和BD的杏仁核中多个PNN群被破坏。聚集素- ir胶质细胞和CS-6-IR胶质“簇”的减少与之前观察到的CSPG/凝集素阳性胶质细胞的增加形成鲜明对比，表明CSPG异常可能影响不同的胶质细胞群，并提示PNN减少的潜在机制。总之，这些异常可能导致突触连通性的不稳定和杏仁核中神经元功能的调节。
Perineuronal nets (PNNs) are specialized extracellular matrix aggregates surrounding distinct neuronal populations and regulating synaptic functions and plasticity. Previous findings showed robust PNN decreases in amygdala, entorhinal cortex and prefrontal cortex of subjects with schizophrenia (SZ), but not bipolar disorder (BD). These studies were carried out using a chondroitin sulfate proteoglycan (CSPG) lectin marker. Here, we tested the hypothesis that the CSPG aggrecan, and 6-sulfated chondroitin sulfate (CS-6) chains highly represented in aggrecan, may contribute to these abnormalities. Antibodies against aggrecan and CS-6 (3B3 and CS56) were used in the amygdala of healthy control, SZ and BD subjects. In controls, aggrecan immunoreactivity (IR) was observed in PNNs and glial cells. Antibody 3B3, but not CS56, also labeled PNNs in the amygdala. In addition, dense clusters of CS56 and 3B3 IR encompassed CS56- and 3B3-IR glia, respectively. In SZ, numbers of aggrecan- and 3B3-IR PNNs were decreased, together with marked reductions of aggrecan-IR glial cells and CS-6 (3B3 and CS56)-IR ‘clusters'. In BD, numbers of 3B3-IR PNNs and CS56-IR clusters were reduced. Our findings show disruption of multiple PNN populations in the amygdala of SZ and, more modestly, BD. Decreases of aggrecan-IR glia and CS-6-IR glial ‘clusters', in sharp contrast to increases of CSPG/lectin-positive glia previously observed, indicate that CSPG abnormalities may affect distinct glial cell populations and suggest a potential mechanism for PNN decreases. Together, these abnormalities may contribute to a destabilization of synaptic connectivity and regulation of neuronal functions in the amygdala of subjects with major psychoses.
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影响因子：
3.3
作者：
Bukalo, O;Schachner, M;Dityatev, A
通讯作者：
Dityatev, A
影响因子：
11
作者：
Buxbaum, J. D.;Georgieva, L.;O'Donovan, M. C.
通讯作者：
O'Donovan, M. C.
影响因子：
3
作者：
Dityatev, Alexander;Brueckner, Gert;Schachner, Melitta
通讯作者：
Schachner, Melitta
影响因子：
2.5
作者：
Carulli, Daniela;Rhodes, Kate E.;Fawcett, James W.
通讯作者：
Fawcett, James W.
影响因子：
3.9
作者：
CATERSON, B;GRIFFIN, J;SORRELL, JM
通讯作者：
SORRELL, JM