高糖刺激受刺激的人星形胶质细胞的神经毒性和炎性细胞因子分泌

Title:High Glucose Enhances Neurotoxicity and Inflammatory Cytokine Secretion by Stimulated Human Astrocytes

Volume: 14 Issue: 7

关键词: 葡萄糖，星形胶质细胞，神经发炎，阿尔茨海默病，2型糖尿病，一β42，高血糖。

摘要: Background: Chronic neuroinflammation caused by activation of microglia and astrocytes in the brain contributes to neuronal loss and disease progression in Alzheimer’s disease (AD). Recent research has identified type 2 diabetes mellitus (T2DM) as a risk factor for AD. High blood glucose (hyperglycemia) and the phenomenon of insulin resistance are being considered as the major factors contributing to an increased risk of AD. However, the mechanisms involved in this interaction remain unclear.

Objective: High glucose has been shown to increase release of pro-inflammatory mediators from various immune cells, including microglia. Since astrocytes are the most abundant glial cell type in the brain, we investigated the effects of elevated glucose concentrations (5.5-30.5 mM) on selected functions of cultured human astrocytes in the presence of inflammatory stimuli.

Method: Experiments were conducted using primary human astrocytes and U-118 MG astrocytoma cells.

Results: High glucose (30.5 mM) increased mRNA expression of interleukin (IL)-6 and secretion of both IL-6 and IL-8 by astrocytes. This astrocytic inflammatory response to high glucose did not appear to be mediated by augmented p38 or p44/42 mitogen activated protein kinase (MAPK) signaling pathways. In addition, high glucose increased the susceptibility of undifferentiated human SH-SY5Y neuronal cells and retinoic-acid differentiated SH-SY5Y cells to injury by hydrogen peroxide (H2O2) and fibrillar amyloid beta-42 protein (Aβ42), respectively.

Conclusion: Our data indicate that hyperglycemia in T2DM may be one of the factors contributing to the observed increased risk of AD by exacerbating astrocyte-mediated neuroinflammation and neuronal injury caused by disease-associated agents.

Cite this article as:

High Glucose Enhances Neurotoxicity and Inflammatory Cytokine Secretion by Stimulated Human Astrocytes, Current Alzheimer Research 2017; 14 (7) . https://dx.doi.org/10.2174/1567205014666170117104053

DOI https://dx.doi.org/10.2174/1567205014666170117104053	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828