Ascorbic acid and α-tocopherol supplement starting prenatally enhances the resistance of nucleus tractus solitarius neurons to hypobaric hypoxic challenge

Abstract

Hypobaric hypoxia, encountered at high altitude, could result in severe consequences. Ascorbic acid (AA) and α-tocopherol (αTC), the two readily available over-the-counter antioxidants, are known to protect nervous tissue against oxidative stress. Here we study whether AA or αTC supplement starting prenatally protects animals against hypobaric hypoxic challenge at adulthood. Expressions of c-fos and the NR1 subunit of the N-methyl-D-aspartate receptors in the nucleus tractus solitarius (NTS) subserving cardiorespiratory functions were investigated. AA and αTC supplement reduced the number of c-fos immunoreactive neurons and intensity of NR1 expression in young and adult animals under normoxia. The treatment, in addition, attenuated the activation of NTS neurons, in terms of c-fos and NR1 expressions, and reduced the anxiety behaviors of adult rats subjected to hypobaric hypoxic challenge. Reduction of c-fos immunoreactive neurons was found concentrated in the chemoreceptor, baroreceptor, and tracheobronchial tree NTS subnuclei that receive corresponding afferents. The protective effect was not found in normal adult animals supplemented with AA or αTC a week before hypobaric hypoxic challenge. In short, prenatal and sustained AA or αTC supplement altered NTS substrate and ameliorated animals' reactions to hypobaric hypoxic insult, suggesting that this may be considered to protect animals from hypoxic insults from young to adult.