Laboratory of Calcium-Binding Proteins in the CNS, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS) Ramio Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
Pos Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, RS, Brazil.
Neurochem Res. 2024 Jul;49(7):1823-1837. doi: 10.1007/s11064-024-04142-8. Epub 2024 May 10.
Methylglyoxal (MG) is considered a classical biomarker of diabetes mellitus and its comorbidities. However, a role for this compound in exacerbated immune responses, such as septicemia, is being increasingly observed and requires clarification, particularly in the context of neuroinflammatory responses. Herein, we used two different approaches (in vivo and acute hippocampal slice models) to investigate MG as a biomarker of neuroinflammation and the neuroimmunometabolic shift to glycolysis in lipopolysaccharide (LPS) inflammation models. Our data reinforce the hypothesis that LPS-induced neuroinflammation stimulates the cerebral innate immune response by increasing IL-1β, a classical pro-inflammatory cytokine, and the astrocyte reactive response, via elevating S100B secretion and GFAP levels. Acute neuroinflammation promotes an early neuroimmunometabolic shift to glycolysis by elevating glucose uptake, lactate release, PFK1, and PK activities. We observed high serum and cerebral MG levels, in association with a reduction in glyoxalase 1 detoxification activity, and a close correlation between serum and hippocampus MG levels with the systemic and neuroinflammatory responses to LPS. Findings strongly suggest a role for MG in immune responses.
甲基乙二醛（MG）被认为是糖尿病及其合并症的经典生物标志物。然而，这种化合物在败血症等加剧的免疫反应中的作用正越来越受到关注，需要加以澄清，特别是在神经炎症反应的背景下。在此，我们使用两种不同的方法（体内和急性海马切片模型）来研究 MG 作为神经炎症的生物标志物以及神经免疫代谢向糖酵解的转变，在脂多糖（LPS）炎症模型中。我们的数据强化了这样一种假设，即 LPS 诱导的神经炎症通过增加白细胞介素-1β（一种经典的促炎细胞因子）和 S100B 分泌和 GFAP 水平，刺激大脑先天免疫反应，从而引发星形胶质细胞的反应性。急性神经炎症通过增加葡萄糖摄取、乳酸释放、PFK1 和 PK 活性，促进早期神经免疫代谢向糖酵解的转变。我们观察到血清和大脑中的 MG 水平升高，与解毒酶 1 （glyoxalase 1）活性降低有关，并且血清和海马中的 MG 水平与 LPS 引起的全身和神经炎症反应密切相关。这些发现强烈表明 MG 在免疫反应中发挥作用。
