Abstract：
People travel to high-altitude regions as tourists, workers, and military personnel on duty. Despite the consistent 21% oxygen content in the atmosphere, ascending to higher altitudes results in a decrease in the partial pressure of oxygen, inducing a state known as hypobaric hypoxia (HH). HH is an environmental stress that is responsible for neuroinflammation and behavioral deficits (anxiety, depression, mood disturbance, etc.), but little is known about its metabolic pathways. The kynurenine pathway (KP) is a promising candidate to uncover the mysteries of HH stress, as it is an important regulator of the immune system and is associated with behavioral deficits. To investigate the role of KP under HH, the levels of KP metabolites in the serum, cerebrospinal fluid (CSF), and brain tissue (prefrontal cortex-PFC, neocortex, and hippocampus) of male Sprague-Dawley rats exposed to HH at 7620 m for 1, 3, and 7 days were estimated utilizing high-performance liquid chromatography (HPLC). The behavioral analogs for anxiety-like and depression-like behavior were assessed using the open field test and forced swim test, respectively. Upon HH exposure, crosstalk between the periphery and central nervous system and KP metabolite region-dependent differential expression in the brain were observed. KP metabolites showed a positive correlation with behavioral parameters. The results of our study are indicative that KP can be proposed as the etiology of behavioral deficits, and KP metabolite levels in serum or CSF can be used as plausible markers for anxiety-like and depression-like behaviors under HH stress with a scope of targeted therapeutic interventions.
摘要：
人们作为游客前往高海拔地区，工人,和当值的军事人员。尽管大气中的氧气含量一致为21%，上升到更高的高度会导致氧气的分压降低，诱导称为低压缺氧（HH）的状态。HH是一种环境压力，导致神经炎症和行为缺陷(焦虑，抑郁症,情绪障碍,等。),但对其代谢途径知之甚少。犬尿氨酸途径（KP）是揭示HH应激奥秘的有希望的候选者，因为它是免疫系统的重要调节剂，并且与行为缺陷有关。为了研究KP在HH下的作用，血清中KP代谢物的水平，脑脊液（CSF），和脑组织(前额叶皮质-PFC，大脑皮层,和海马）使用高效液相色谱（HPLC）估算了在7620m下暴露于HH的雄性Sprague-Dawley大鼠的1、3和7天。使用野外测试和强迫游泳测试评估了焦虑样和抑郁样行为的行为类似物，分别。HH暴露后,观察到外周和中枢神经系统之间的串扰以及大脑中KP代谢物区域依赖性的差异表达。KP代谢产物与行为参数呈正相关。我们的研究结果表明，可以提出KP作为行为缺陷的病因，血清或CSF中的KP代谢物水平可以用作HH应激下焦虑样和抑郁样行为的合理标志物，并具有针对性的治疗干预范围。
