2-Deoxyglucose alleviates migraine-related behaviors by modulating microglial inflammatory factors in experimental model of migraine

BackgroundTargeting metabolic pathways has emerged as a new migraine treatment strategy as researchers realize the critical role metabolism plays in migraine. Activated inflammatory cells undergo metabolic reprogramming and rely on glycolysis to function. The objective of this study was to investigate the glycolysis changes in the experimental model of migraine and the effect of glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) in the pathophysiology of migraine.MethodsWe used a rat model of migraine that triggered migraine attacks by applying inflammatory soup (IS) to the dura and examined changes in glycolysis. 2-DG was used to inhibit glycolysis, and the effects of 2-DG on mechanical ectopic pain, microglial cell activation, calcitonin gene-related peptides (CGRP), c-Fos, and inflammatory factors induced by inflammatory soup were observed. LPS stimulated BV2 cells to establish a model in vitro to observe the effects of 2-DG on brain-derived neurotrophic factor (BDNF) after microglia activation.ResultsIn the experimental model of migraine, key enzymes involved in glycolysis such as phosphofructokinase platelet (PFKP), hexokinase (HK2), hypoxia inducible factor-1α (HIF-1α), lactate dehydrogenase (LDH) and pyruvate kinase (PKM2) were expressed in the medullary dorsal horn. While the expression of electronic respiratory transport chain complex IV (COXIV) decreased. There were no significant changes in glucose 6-phosphate dehydrogenase (G6PD), a key enzyme in the pentose phosphate pathway. The glycolysis inhibitor 2-DG alleviated migraine-like symptoms in an experimental model of migraine, reduced the release of proinflammatory cytokines caused by microglia activation, and decreased the expression of CGRP and c-Fos. Further experiments in vitro demonstrated that glycolysis inhibition can reduce the release of Iba-1/proBDNF/BDNF and inhibit the activation of microglia.ConclusionThe migraine rat model showed enhanced glycolysis. This study suggests that glycolytic inhibitor 2-DG is an effective strategy for alleviating migraine-like symptoms. Glycolysis inhibition may be a new target for migraine treatment

Impacts of climate change and fruit tree expansion on key hydrological components at different spatial scales

Assessing how fruit tree expansion and climate variability affect hydrological components (e.g., water yield, surface runoff, underground runoff, soil water, evapotranspiration, and infiltration) at different spatial scales is crucial for the management and protection of watersheds, ecosystems, and engineering design. The Jiujushui watershed (259.32 km2), which experienced drastic forest changes over the past decades, was selected to explore the response mechanisms of hydrological components to fruit tree expansion and climate variability at different spatial scales (whole basin and subbasin scale). Specifically, we set up two change scenarios (average temperature increase of 0.5°C and fruit tree area expansion of 18.97%) in the SWAT model by analyzing historical data (1961∼2011). Results showed that climate change reduced water yield, surface runoff, and underground runoff by 6.75, 0.37, and 5.91 mm, respectively. By contrast, the expansion of fruit trees increased surface runoff and water yield by 2.81 and 4.10 mm, respectively, but decreased underground runoff by 1 mm. Interestingly, the sub-basins showed different intensities and directions of response under climate change and fruit tree expansion scenarios. However, the downstream response was overall more robust than the upstream response. These results suggest that there may be significant differences in the hydrological effects of climate change and fruit tree expansion at different spatial scales, thus any land disturbance measures should be carefully considered