Increased inflammasome protein expression identified in microglia from postmortem brains with schizophrenia.

IF 3.2 3区 医学 Q2 CLINICAL NEUROLOGY Journal of Neuropathology and Experimental Neurology Pub Date : 2024-11-01 DOI:10.1093/jnen/nlae066
Ryan Gober, Julian Dallmeier, David Davis, Daniel Brzostowicki, Juan Pablo de Rivero Vaccari, Brianna Cyr, Ayled Barreda, Xiaoyan Sun, Sakir Humayun Gultekin, Susanna Garamszegi, William Scott, Regina Vontell
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Abstract

Schizophrenia (SCZ) is a complex psychiatric disorder that involves an inflammatory response thought to be characterized by microglial activation. The inflammasome complex may play critical roles in the pathomechanism of neuroinflammation but how this relates to SCZ remains unclear. In this study, we performed an immunohistochemical (IHC) analysis to compare the expression of inflammasome proteins in brain tissue from donors with SCZ (n = 16) and non-psychiatric donors (NP; n = 13) isolated from the superior frontal cortex (SFC), superior temporal cortex, and anterior cingulate cortex brain regions. To assess changes in the cell populations that express key inflammasome proteins, we performed IHC analyses of apoptosis-associated speck-like protein containing a CARD (ASC), nod-like receptor protein 3 (NLRP3), and interleukin (IL)-18 to determine if these proteins are expressed in microglia, astrocytes, oligodendrocytes, or neurons. Inflammasome proteins were expressed mainly in microglia from SCZ and NP brains. Increased numbers of microglia were present in the SFC of SCZ brains and exhibited higher inflammasome protein expression of ASC, NLRP3, and IL-18 compared to NPs. These findings suggest that increased inflammasome signaling may contribute to the pathology underlying SCZ.

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在精神分裂症患者死后大脑的小胶质细胞中发现炎性体蛋白表达增加。
精神分裂症(SCZ)是一种复杂的精神疾病,涉及一种被认为以小胶质细胞活化为特征的炎症反应。炎性体复合物可能在神经炎症的病理机制中发挥关键作用,但它与精神分裂症的关系尚不清楚。在这项研究中,我们进行了免疫组化(IHC)分析,比较了从上额叶皮层(SFC)、上颞叶皮层和前扣带皮层脑区分离出的患有SCZ的供体(n = 16)和非精神病供体(NP;n = 13)的脑组织中炎性体蛋白的表达。为了评估表达关键炎症小体蛋白的细胞群的变化,我们对含有CARD的凋亡相关斑点样蛋白(ASC)、类结节受体蛋白3(NLRP3)和白细胞介素(IL)-18进行了IHC分析,以确定这些蛋白是否在小胶质细胞、星形胶质细胞、少突胶质细胞或神经元中表达。炎症小体蛋白主要在SCZ和NP大脑的小胶质细胞中表达。与NPs相比,SCZ大脑的SFC中存在更多的小胶质细胞,并表现出更高的炎性体蛋白ASC、NLRP3和IL-18表达量。这些发现表明,炎性体信号的增加可能是导致SCZ的病理基础。
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来源期刊
CiteScore
5.40
自引率
6.20%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Journal of Neuropathology & Experimental Neurology is the official journal of the American Association of Neuropathologists, Inc. (AANP). The journal publishes peer-reviewed studies on neuropathology and experimental neuroscience, book reviews, letters, and Association news, covering a broad spectrum of fields in basic neuroscience with an emphasis on human neurological diseases. It is written by and for neuropathologists, neurologists, neurosurgeons, pathologists, psychiatrists, and basic neuroscientists from around the world. Publication has been continuous since 1942.
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