L-DOPA regulates neuroinflammation and Aβ pathology through NEP and ADAM17 in a mouse model of AD

IF 3.3 3区医学 Q2 NEUROSCIENCES

Molecular Brain Pub Date : 2024-04-30 DOI:10.1186/s13041-024-01092-8

Hyun-ju Lee, JinHan Nam, Jeong-Woo Hwang, Jin-Hee Park, Yoo Joo Jeong, Ji-Yeong Jang, Su-Jeong Kim, A-Ran Jo, Hyang-Sook Hoe

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引用次数: 0

Abstract

Dopamine plays important roles in cognitive function and inflammation and therefore is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Drugs that increase or maintain dopamine levels in the brain could be a therapeutic strategy for AD. However, the effects of dopamine and its precursor levodopa (L-DOPA) on Aβ/tau pathology in vivo and the underlying molecular mechanisms have not been studied in detail. Here, we investigated whether L-DOPA treatment alters neuroinflammation, Aβ pathology, and tau phosphorylation in 5xFAD mice, a model of AD. We found that L-DOPA administration significantly reduced microgliosis and astrogliosis in 5xFAD mice. In addition, L-DOPA treatment significantly decreased Aβ plaque number by upregulating NEP and ADAM17 levels in 5xFAD mice. However, L-DOPA-treated 5xFAD mice did not exhibit changes in tau hyperphosphorylation or tau kinase levels. These data suggest that L-DOPA alleviates neuroinflammatory responses and Aβ pathology but not tau pathology in this mouse model of AD.

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在一种注意力缺失症小鼠模型中，L-DOPA 通过 NEP 和 ADAM17 调节神经炎症和 Aβ 病理变化

多巴胺在认知功能和炎症中发挥着重要作用，因此与包括阿尔茨海默病（AD）在内的神经退行性疾病的发病机制有关。增加或维持大脑中多巴胺水平的药物可能是治疗阿尔茨海默病的一种策略。然而，多巴胺及其前体左旋多巴（L-DOPA）对体内Aβ/tau病理学的影响及其潜在的分子机制尚未得到详细研究。在这里，我们研究了L-DOPA治疗是否会改变5xFAD小鼠（一种AD模型）的神经炎症、Aβ病理学和tau磷酸化。我们发现，服用 L-DOPA 能显著减少 5xFAD 小鼠的小胶质细胞和星形胶质细胞增生。此外，通过上调 NEP 和 ADAM17 的水平，L-DOPA 还能明显减少 5xFAD 小鼠体内 Aβ 斑块的数量。然而，经 L-DOPA 处理的 5xFAD 小鼠并没有表现出 tau 过度磷酸化或 tau 激酶水平的变化。这些数据表明，L-DOPA 可减轻这种 AD 小鼠模型的神经炎症反应和 Aβ 病理变化，但不能减轻 tau 病理变化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Brain NEUROSCIENCES-

CiteScore

7.30

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.