Dataset Information

Liver CEBP? Modulates the Kynurenine Metabolism and Mediates the Motility for Hypoxia-Induced Central Fatigue in Mice.

ABSTRACT: Central fatigue is defined as a failure of the central nervous system to adequately drive the muscle, manifesting limited development, and maintenance of locomotor activity. A plateau in hypoxia leads to central fatigue and followed by maximal motility recession. However, the underlying mechanism is still unclear. The present study describes a mechanism by which liver CEBP? (CCAAT/enhancer-binding protein beta) induced by hypoxic environment alters the kynurenine (KYN) metabolism and causes the suppression of motility function recession. The activation of CEBP? under hypoxia increases the liver expression of tryptophan dioxygenase, thereby enhancing the conversion of tryptophan into KYN; the KYN metabolite can traverse the blood-brain barrier and result in the suppression of motility function. However, the knockdown of CEBP? by injecting pAAV-shRNA-CEBP? via the hepatic portal vein reduces the KYN production and improves the motility function. KYN is a neurochemical that which restricts the exercise capacity after injection in the basal ganglia in mice. Reducing the plasma KYN protects the brain from hypoxia-induced changes associated with fatigue, and the knockdown liver of CEBP? in mice renders resistance to fatigue post-acute hypoxia or tryptophan treatment. This study reveals resistance to central fatigue as a strategy for acclimatization to hypoxia mediated by transcription factor CEBP? in the liver.

SUBMITTER: Yang F

PROVIDER: S-EPMC6428026 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Liver CEBPβ Modulates the Kynurenine Metabolism and Mediates the Motility for Hypoxia-Induced Central Fatigue in Mice.

Yang Fan F Zhou Li L Song Jun J WangJinMei A A Yang Yuan Y Tang Zhong-Wei ZW Huang Qing-Yuan QY

Frontiers in physiology 20190314

Central fatigue is defined as a failure of the central nervous system to adequately drive the muscle, manifesting limited development, and maintenance of locomotor activity. A plateau in hypoxia leads to central fatigue and followed by maximal motility recession. However, the underlying mechanism is still unclear. The present study describes a mechanism by which liver CEBPβ (CCAAT/enhancer-binding protein beta) induced by hypoxic environment alters the kynurenine (KYN) metabolism and causes the ...[more]

PMID: 30930794

Similar Datasets

Project description:BackgroundDisturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD.MethodsThirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites.ResultsSubtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry.DiscussionIn addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD.

Dataset Information

Liver CEBP? Modulates the Kynurenine Metabolism and Mediates the Motility for Hypoxia-Induced Central Fatigue in Mice.

Publications

Liver CEBPβ Modulates the Kynurenine Metabolism and Mediates the Motility for Hypoxia-Induced Central Fatigue in Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets