Gene Expression Changes in a Model Neuron Cell Line Exposed to Autoantibodies from Patients with Traumatic Brain Injury and/or Type 2 Diabetes.
Gene Expression Changes in a Model Neuron Cell Line Exposed to Autoantibodies from Patients with Traumatic Brain Injury and/or Type 2 Diabetes.
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外伤性脑损伤和/或2型糖尿病患者自身抗体暴露的模型神经元细胞系基因表达变化
DOI：
10.1007/s12035-021-02428-4
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发表时间：
2021-09
影响因子：
5.1
通讯作者：
Citron BA
中科院分区：
文献类型：
--
作者：
Zimering MB;Delic V;Citron BA
创伤性脑损伤和成人2型糖尿病均通过未知机制与晚期发生的加速认知衰退和帕金森病相关。此前，我们报告了帕金森病、痴呆症和患有微血管并发症的糖尿病患者子集血浆中针对5-羟色胺2A受体的循环激动剂自身抗体增加。在这里，我们使用一个模型神经元，小鼠神经母细胞瘤（N2 A）细胞系，测试信使RNA表达的变化后，短暂暴露于创伤性脑损伤和/或2型糖尿病血浆窝藏激动剂5-羟色胺2A受体自身抗体。我们现在报告线粒体功能障碍途径和帕金森病途径参与神经母细胞瘤细胞中发生的自身抗体诱导的基因表达变化。显著上调的功能基因类别包括细胞死亡、细胞骨架-微管功能、肌动蛋白聚合或解聚、细胞氧化应激调节、线粒体功能、免疫功能、蛋白质代谢和囊泡功能。显著下调的基因类别包括微管功能、细胞粘附、神经递质释放、多巴胺代谢突触可塑性、维持神经元分化、线粒体功能和细胞信号传导。总之，这些结果表明，激动剂5-羟色胺受体自身抗体（其在帕金森病和其他形式的神经变性中增加）介导模型神经元中基因表达变化的协调程序，其易发生神经细胞凋亡并与人类神经变性疾病途径相关。
Traumatic brain injury and adult type 2 diabetes mellitus are each associated with the late occurrence of accelerated cognitive decline and Parkinson’s disease through unknown mechanisms. Previously, we reported increased circulating agonist autoantibodies targeting the 5-hydroxytryptamine 2A receptor in plasma from subsets of Parkinson’s disease, dementia, and diabetic patients suffering with microvascular complications. Here, we use a model neuron, mouse neuroblastoma (N2A) cell line, to test messenger RNA expression changes following brief exposure to traumatic brain injury and/or type 2 diabetes mellitus plasma harboring agonist 5-hydroxytryptamine 2A receptor autoantibodies. We now report involvement of the mitochondrial dysfunction pathway and Parkinson’s disease pathways in autoantibody-induced gene expression changes occurring in neuroblastoma cells. Functional gene categories upregulated significantly included cell death, cytoskeleton-microtubule function, actin polymerization or depolymerization, regulation of cell oxidative stress, mitochondrial function, immune function, protein metabolism, and vesicle function. Gene categories significantly downregulated included microtubule function, cell adhesion, neurotransmitter release, dopamine metabolism synaptic plasticity, maintenance of neuronal differentiation, mitochondrial function, and cell signaling. Taken together, these results suggest that agonist 5-hydroxytryptamine receptor autoantibodies (which increase in Parkinson’s disease and other forms of neurodegeneration) mediate a coordinating program of gene expression changes in a model neuron which predispose to neuro-apoptosis and are linked to human neurodegenerative diseases pathways.
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DOI：
10.1006/bbrc.1993.1072
发表时间：
1993-01-29
影响因子：
3.1
作者：
PARRUTI, G;AMBROSINI, G;DEBLASI, A
通讯作者：
DEBLASI, A
影响因子：
4.8
作者：
Walker KR;Tesco G
通讯作者：
Tesco G
影响因子：
4.7
作者：
SCHAPIRA, AHV;COOPER, JM;MARSDEN, CD
通讯作者：
MARSDEN, CD
影响因子：
64.5
作者：
MCMAHON, HT;MISSLER, M;SUDHOF, TC
通讯作者：
SUDHOF, TC
DOI：
10.1212/01.con.0000436152.24038.e0
发表时间：
2013-10-01
期刊：
Continuum (Minneapolis, Minn.)
影响因子：
--
作者：
Williams, David R;Litvan, Irene
通讯作者：
Litvan, Irene