AUTHOR=Zheng Xiang , Bi Wenjie , Yang Guizhi , Zhao Jia , Wang Jie , Li Xiaojing , Zhou Xue TITLE=Hyperglycemia Induced by Chronic Restraint Stress in Mice Is Associated With Nucleus Tractus Solitarius Injury and Not Just the Direct Effect of Glucocorticoids JOURNAL=Frontiers in Neuroscience VOLUME=12 YEAR=2018 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00983 DOI=10.3389/fnins.2018.00983 ISSN=1662-453X ABSTRACT=

Chronic restraint stress (CRS) can affect hypothalamic-pituitary-adrenal (HPA) axis activity and increase glucocorticoid levels. Glucocorticoids are stress hormones that regulate multiple aspects of energy homeostasis. Stress also impairs glucose tolerance. The aim of this study was to investigate the cause of insulin-resistant hyperglycemia during CRS. We produced the CRS models (a 7-day restraint followed by a 3-day free moving procedure, total of 4 cycles for 40 days) in mice, detected the parameters related to glucose metabolism, and compared them to those of the dexamethasone (DEX) injection (0.2 mg/kg i.p., also a 4 cycle procedure as the CRS). The results showed that the CRS induced a moderate (not higher than 11 mmol/L) and irreversible insulin-resistant hyperglycemia in about 1/3 of the individuals, and all the restrained mice had adrenal hypertrophy. CRS induced the apoptosis of neurons in the anterior part of commissural subnucleus of nucleus tractus solitarius (acNTS) in the hyperglycemic mice, and acNTS mechanical damage also led to insulin-resistant hyperglycemia. In contrast, in the DEX-treated mice, adrenal gland atrophy was evident. The glucose and insulin tolerance varied with the delay of determination. DEX exposure in vivo does not induce the apoptosis of neurons in NTS. This study indicates that restraint stress and DEX induce metabolic disorders through different mechanisms. During CRS, injury (apoptosis) of glucose-sensitive acNTS neurons cause dysregulation of blood glucose. This study also suggests the mouse restraint stress model has value as a potential application in the study of stress-induced hyperglycemia.