Bhattacharjee Monojit, Manoharan Suryaa, Deshetty Uma Maheswari, Perumal Ekambaram
DRDO-BU Centre for Life Sciences, Bharathiar University, Coimbatore, 641 046, India.
Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, India.
Neurochem Res. 2023 Feb;48(2):471-486. doi: 10.1007/s11064-022-03767-x. Epub 2022 Oct 7.
Hypoxia is a state in which the body or a specific part of the body is deprived of adequate oxygen supply at the tissue level. Sojourners involved in different activities at high altitudes (> 2500 m) face hypobaric hypoxia (HH) due to low oxygen in the atmosphere. HH is an example of generalized hypoxia, where the homeostasis of the entire body of an organism is affected and results in neurochemical changes. It is known that lower O levels affect catecholamines (CA), severely impairing cognitive and locomotor behavior. However, there is less evidence on the effect of HH-mediated alteration in brain Tetrahydrobiopterin (BH4) levels and its role in neurobehavioral impairments. Hence, this study aimed to shed light on the effect of acute HH on CA and BH4 levels with its neurobehavioral impact on Wistar rat models. After HH exposure, significant alteration of the CA levels in the discrete brain regions, viz., frontal cortex, hippocampus, midbrain, and cerebellum was observed. HH exposure significantly reduced spontaneous motor activity, motor coordination, and spatial memory. The present study suggests that the HH-induced behavioral changes might be related to the alteration of the expression pattern of CA and BH4-related genes and proteins in different rat brain regions. Overall, this study provides novel insights into the role of BH4 and CA in HH-induced neurobehavioral impairments.
缺氧是一种身体或身体特定部位在组织水平上被剥夺充足氧气供应的状态。在高海拔地区（>2500米）参与不同活动的旅居者由于大气中氧气含量低而面临低压缺氧（HH）。HH是全身性缺氧的一个例子，在此情况下生物体整个身体的稳态受到影响并导致神经化学变化。已知较低的氧水平会影响儿茶酚胺（CA），严重损害认知和运动行为。然而，关于HH介导的脑四氢生物蝶呤（BH4）水平改变及其在神经行为损伤中的作用的证据较少。因此，本研究旨在阐明急性HH对CA和BH4水平的影响及其对Wistar大鼠模型的神经行为影响。HH暴露后，在离散脑区，即额叶皮质、海马体、中脑和小脑中观察到CA水平的显著改变。HH暴露显著降低了自发运动活动、运动协调性和空间记忆。本研究表明，HH诱导的行为变化可能与不同大鼠脑区中CA和BH4相关基因及蛋白质表达模式的改变有关。总体而言，本研究为BH4和CA在HH诱导的神经行为损伤中的作用提供了新的见解。
