Different changes in cortical tumor necrosis factor-α-related pathways in schizophrenia and mood disorders
Different changes in cortical tumor necrosis factor-α-related pathways in schizophrenia and mood disorders
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DOI：
10.1038/mp.2012.95
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发表时间：
2013-07-01
影响因子：
11
通讯作者：
Scarr, E.
中科院分区：
文献类型：
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作者：
Dean, B.;Gibbons, A. S.;Scarr, E.
越来越多的证据表明肿瘤坏死因子-α(TNF-α)与精神疾病的病理生理学有关，这促使我们测量了患有严重抑郁障碍(MDD)的受试者大脑皮质中该蛋白的水平。据报道，在患有这种疾病的人中，Brodmann区(BA)46而不是24的跨膜形式(tmTNFα)水平增加了(458%)，但可溶性形式(sTNFα)却没有增加，我们决定在MDD患者的相同区域检测与TNFα相关的其他成分，并将我们的研究扩展到精神分裂症(Sz)和双相情感障碍(BD)患者的相同皮质区域。利用死后组织、免疫印迹和定量聚合酶链式反应，我们现在已经表明，在BD受试者的Brodmann区24区，tmTNFα显著增加(305%)，而在Sz区，tmTNFα的水平没有改变。BD组和Sz组sTNF-α水平无明显变化。此外，我们还发现，Sz患者BA24(53%)和BA46(82%)的肿瘤坏死因子受体1(TNFR1)mRNA水平升高，而心境障碍患者BA46(MDD=-51%；BD=-67%)的TNFR2 mRNA水平降低。在情绪障碍患者的大脑皮层中，经常被用作神经元、星形胶质细胞和小胶质细胞数量替代标志物的蛋白质水平，以及促炎标志物(白介素1β)的水平没有改变。我们的数据表明，MDD、BD和Sz患者大脑皮质中存在不同的TNFα相关标记物的变化，这些变化可能与经典炎症无关，并可能导致不同的TNFα相关信号通路的变化。
The growing body of evidence implicating tumor necrosis factor-alpha (TNF alpha) in the pathophysiology of psychiatric disorders led us to measure levels of that protein in the cortex of subjects with major depressive disorders (MDD). Having reported an increase (458%) in the levels of the transmembrane (tmTNF alpha), but not the soluble (sTNF alpha), form of the protein in Brodmann's area (BA) 46, but not 24, in people with the disorder, we decided to examine additional components of TNF alpha-related pathways in the same regions in people with MDD and extend our studies to the same cortical regions of people with schizophrenia (Sz) and bipolar disorders (BD). Using postmortem tissue, western blots and quantitative PCR, we have now shown there is a significant increase (305%) in tmTNF alpha in Brodmann's area 24, but not 46, from subjects with BD, and that levels of the protein were not altered in Sz. Levels of sTNF alpha were not altered in BD or Sz. In addition, we have shown that levels of TNF receptor 1 (TNFR1) mRNA are increased in BA 24 (53%) and BA 46 (82%) in people with Sz, whereas levels of TNFR2 mRNA was decreased in BA 46 in people with mood disorders (MDD = -51%; BD = -67%). Levels of proteins frequently used as surrogate markers of neuronal, astrocytic and microglia numbers, as well as levels of the pro-inflammatory marker (interleukin 1 beta), were not changed in the cortex of people with mood disorders. Our data suggest there are differential changes in TNF alpha-related markers in the cortex of people with MDD, BD and Sz that may not be related to classical inflammation and may cause changes in different TNF alpha-related signaling pathways.