几丁质酶-3 类蛋白-1 与多发性硬化症神经元衰退的关系

IF 3.9 4区 医学 Q2 NEUROSCIENCES ASN NEURO Pub Date : 2023-01-01 DOI:10.1177/17590914231198980
Intakhar Ahmad, Stig Wergeland, Eystein Oveland, Lars Bø
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引用次数: 0

摘要

甲壳素酶-3样蛋白-1(CHI3L1)在脑脊液中的水平升高与多发性硬化症(MS)患者的炎症活动和疾病进展有关。本研究旨在调查CHI3L1在多发性硬化症患者大脑和小鼠铜绿素模型(CPZ)中的存在情况,铜绿素模型是一种毒性/代谢性脱髓鞘和不同脑区再髓鞘化的模型。在多发性硬化症灰质(GM)中,主要在星形胶质细胞和锥体神经元亚群中检测到 CHI3L1。在神经元中,CHI3L1免疫阳性与脂褐素样物质的积累有关,脂褐素样物质是细胞衰老的标志,可导致细胞死亡。与对照组相比,正常表现的 MS GM 组织中 CHI3L1 阳性神经元的密度明显更高(p = .014)。在多发性硬化症白质(WM)中,位于病变区域内的星形胶质细胞、血管周围的正常外观区域以及病变发展初期的吞噬细胞中都检测到了 CHI3L1。在 CPZ 模型中,CHI3L1 阳性细胞的密度与 WM 中的小胶质细胞活化和脉络丛炎症密切相关。与对照组相比,CHI3L1在WM中的免疫阳性率从CPZ暴露的早期阶段就开始增加。在基因组中,CHI3L1免疫阳性反应在CPZ暴露阶段的后期增加,尤其是在基因组深部区域。这些结果表明,CHI3L1 与多发性硬化症的神经元退化、病变前病理和炎症有关。
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An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis.

Elevated levels of Chitinase-3-like protein-1 (CHI3L1) in cerebrospinal fluid have previously been linked to inflammatory activity and disease progression in multiple sclerosis (MS) patients. This study aimed to investigate the presence of CHI3L1 in the brains of MS patients and in the cuprizone model in mice (CPZ), a model of toxic/metabolic demyelination and remyelination in different brain areas. In MS gray matter (GM), CHI3L1 was detected primarily in astrocytes and in a subset of pyramidal neurons. In neurons, CHI3L1 immunopositivity was associated with lipofuscin-like substance accumulation, a sign of cellular aging that can lead to cell death. The density of CHI3L1-positive neurons was found to be significantly higher in normal-appearing MS GM tissue compared to that of control subjects (p  =  .014). In MS white matter (WM), CHI3L1 was detected in astrocytes located within lesion areas, as well as in perivascular normal-appearing areas and in phagocytic cells from the initial phases of lesion development. In the CPZ model, the density of CHI3L1-positive cells was strongly associated with microglial activation in the WM and choroid plexus inflammation. Compared to controls, CHI3L1 immunopositivity in WM was increased from an early phase of CPZ exposure. In the GM, CHI3L1 immunopositivity increased later in the CPZ exposure phase, particularly in the deep GM region. These results indicate that CHI3L1 is associated with neuronal deterioration, pre-lesion pathology, along with inflammation in MS.

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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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