Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Sacramento, CA, USA; Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, USA.
Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Sacramento, CA, USA; Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA, USA.
Parkinsonism Relat Disord. 2021 Jan;82:117-120. doi: 10.1016/j.parkreldis.2020.11.026. Epub 2020 Nov 30.
Fragile X Tremor and Ataxia Syndrome is a progressive neurodegenerative disorder that develops in some FMR1 premutation carriers. The objective of this study is to characterize how cytokine levels are altered in the FXTAS brain.
Fresh frozen cerebellar tissue from FXTAS cases and controls was homogenized and analyzed for 12 different cytokines using a commercially available ELISA panel.
Relative to controls, FXTAS cases showed large and significant increases in the cytokines IL-12 and TNFα. There were large but non-significant increases in the levels of IL-2, IL-8, and IL-10 in FXTAS cases. The cytokines IL-1A, IL-1B, IL-4 IL-6, IL-17A, IFNγ, and GM-CSF were not different between FXTAS and control subjects.
For the first time, we demonstrate an increase in the pro-inflammatory cytokines TNFα and IL-12 in the FXTAS brain, both of which are implicated in the pathogenesis of Multiple Sclerosis, another neurodegenerative disorder that predominantly consists of white matter disease.
脆性 X 震颤共济失调综合征是一种进行性神经退行性疾病,在一些 FMR1 前突变携带者中发展。本研究的目的是描述 FXTAS 大脑中细胞因子水平如何发生改变。
使用商业上可用的 ELISA 试剂盒,对 FXTAS 病例和对照者的新鲜冷冻小脑组织进行匀浆分析,以检测 12 种不同的细胞因子。
与对照组相比,FXTAS 病例中细胞因子 IL-12 和 TNFα 的水平显著升高。FXTAS 病例中 IL-2、IL-8 和 IL-10 的水平也显著升高,但无统计学意义。细胞因子 IL-1A、IL-1B、IL-4、IL-6、IL-17A、IFNγ 和 GM-CSF 在 FXTAS 和对照组之间没有差异。
我们首次证明 FXTAS 大脑中促炎细胞因子 TNFα 和 IL-12 的增加,这两种细胞因子都与多发性硬化症的发病机制有关,多发性硬化症是另一种主要由白质疾病组成的神经退行性疾病。