Herrera Solis Brandon Isai, Guerrero-Padilla Frida, Mera Jiménez Elvia, Vega López Juan Manuel, Perea-Flores María de Jesús, Rodríguez-Cortés Octavio, Macías Pérez Martha Edith, Hernández-Rodríguez Maricarmen
Laboratorio de Cultivo Celular, Neurofarmacología y Conducta, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico.
Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico.
Brain Sci. 2025 Sep 1;15(9):952. doi: 10.3390/brainsci15090952.
Metabolic memory refers to the long-term adverse effects of short-term disturbances in glucose metabolism. Recent evidence indicates that hyperglycemia-induced metabolic memory contributes to sustained cellular damage even after glycemic control, driven by increased production of reactive oxygen species (ROS), activation of inflammatory pathways, and accumulation of advanced glycation end products (AGEs). Although well characterized in endothelial and smooth muscle cells, this phenomenon may also occur in other cell types, including glial cells. This study aimed to evaluate the persistence of high-glucose (HG)-induced alterations after returning to normal glucose (NG) conditions in primary mixed glial cell (MGC) cultures. Primary MGCs were obtained from neonatal Wistar rat pups and cultured under three conditions for 21 days: NG (5.5 mM glucose), HG (25 mM glucose), and HG-NG (14 days in HG followed by 7 days in NG). Cell proliferation, apoptosis, ROS production, lipid peroxidation, mitochondrial activity, TNF-α, IL-6, and AGE formation were assessed. MGCs cultured under HG and HG-NG conditions exhibited reduced proliferation without increased apoptosis. Both HG and HG-NG conditions promoted ROS overproduction accompanied by reduced mitochondrial activity, whereas only HG increased lipid peroxidation. Notably, TNF-α and AGE levels were elevated in both HG and HG-NG conditions, while IL-6 production decreased exclusively in HG-NG. These findings demonstrate the persistence of deleterious effects induced by HG in MGCs, even after restoration to NG conditions.
代谢记忆是指葡萄糖代谢短期紊乱的长期不良影响。最近的证据表明，即使在血糖得到控制后，高血糖诱导的代谢记忆仍会导致细胞持续受损，这是由活性氧（ROS）生成增加、炎症途径激活和晚期糖基化终产物（AGEs）积累所驱动的。尽管这种现象在内皮细胞和平滑肌细胞中已有充分描述，但它也可能发生在其他细胞类型中，包括神经胶质细胞。本研究旨在评估原代混合神经胶质细胞（MGC）培养物在恢复到正常葡萄糖（NG）条件后，高糖（HG）诱导的改变的持续性。原代MGC取自新生Wistar大鼠幼崽，并在三种条件下培养21天：NG（5.5 mM葡萄糖）、HG（25 mM葡萄糖）和HG-NG（先在HG中培养14天，然后在NG中培养7天）。评估细胞增殖、凋亡、ROS生成、脂质过氧化、线粒体活性、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和AGE形成。在HG和HG-NG条件下培养的MGC增殖减少，但凋亡未增加。HG和HG-NG条件均促进ROS过量生成，同时线粒体活性降低，而只有HG增加脂质过氧化。值得注意的是，HG和HG-NG条件下TNF-α和AGE水平均升高，而IL-6生成仅在HG-NG中减少。这些发现表明，即使恢复到NG条件后，HG在MGC中诱导的有害影响仍然持续存在。
