Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, CP 04510, Mexico.
Departamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, CP 14269, Mexico.
Oxid Med Cell Longev. 2021 Nov 8;2021:3790477. doi: 10.1155/2021/3790477. eCollection 2021.
Low-ozone doses cause alterations in the oxidation-reduction mechanisms due to the increase in reactive oxygen species, alter cell signaling, and produce deleterious metabolic responses for cells. Adenosine 5'triphosphate (ATP) can act as a mediator in intercellular communication between neurons and glial cells. When there is an increase in extracellular ATP, a modification is promoted in the regulation of inflammation, energy metabolism, by affecting the intracellular signaling pathways that participate in these processes. The objective of this work was to study changes in the P2X7 receptor, and their relationship with the inflammatory response and energy metabolism, in a model of progressive neurodegeneration in the hippocampus of rats chronically exposed to low-ozone doses. Therefore, 72 male rats were exposed to low-ozone doses for different periods of time. After exposure to ozone was finished, rats were processed for immunohistochemical techniques, western blot, quantitative polymerase chain reaction (qPCR), and histological techniques for periodic acid-Schiff staining. The results showed immunoreactivity changes in the amount of the P2X7 protein. There was an increase in phosphorylation for glycogen synthase kinase 3- (GSK3-) as treatment continued. There were also increases in 27 interleukin 1 beta (IL-1 ) and interleukin 17 (IL-17) and a decrease in interleukin 10 (IL-10). Furthermore, neuronal glycogen was found at 30 and 60 days, and an increase in caspase 3. An increase in mRNA was also shown for the P2X7 gene at 60 days, and GSK3- at 90 days of exposure. In conclusion, these results suggest that repeated exposure to low-ozone doses, such as those that can occur during highly polluted days, causes a state of oxidative stress, leading to alterations in the P2X7 receptors, which promote changes in the activation of signaling pathways for inflammatory processes and cell death, converging at a progressive neurodegeneration process, as may be happening in Alzheimer's disease.
低浓度臭氧会导致氧化还原机制的改变，因为活性氧物种的增加会改变细胞信号转导，并对细胞产生有害的代谢反应。三磷酸腺苷 (ATP) 可以作为神经元和神经胶质细胞之间细胞间通讯的介质。当细胞外 ATP 增加时，通过影响参与这些过程的细胞内信号通路，会促进炎症、能量代谢的调节。本工作的目的是研究在慢性暴露于低浓度臭氧剂量的大鼠海马进行性神经退行性变模型中，P2X7 受体的变化及其与炎症反应和能量代谢的关系。因此，72 只雄性大鼠暴露于低浓度臭氧剂量不同的时间。暴露于臭氧结束后，对大鼠进行免疫组织化学技术、western blot、定量聚合酶链反应（qPCR）和过碘酸希夫染色的组织学技术处理。结果显示 P2X7 蛋白的免疫反应性发生变化。随着治疗的继续，糖原合酶激酶 3-（GSK3-）的磷酸化增加。白细胞介素 1β（IL-1β）和白细胞介素 17（IL-17）增加，白细胞介素 10（IL-10）减少。此外，在 30 和 60 天发现神经元糖原，并增加 caspase 3。在 60 天还显示 P2X7 基因和 GSK3-的 mRNA 增加，在 90 天暴露时增加。总之，这些结果表明，反复暴露于低浓度臭氧，如在高度污染的日子里可能发生的那样，会导致氧化应激状态，导致 P2X7 受体发生改变，从而促进炎症过程和细胞死亡的信号通路的激活发生变化，导致进行性神经退行性变过程，这可能发生在阿尔茨海默病中。
