BST Stimulation Induces Atrophy and Changes in Aerobic Energy Metabolism in Rat Skeletal Muscles-The Biphasic Action of Endogenous Glucocorticoids.

Jan Jacek Kaczor,Mateusz Jakub Karnia,Magdalena Podlacha,Dorota Myślińska,Katarzyna Patrycja Dzik,Damian Józef Flis

doi:10.3390/ijms21082787

Abstract

(1) The primary involvement in stress-induced disturbances in skeletal muscles is assigned to the release of glucocorticoids (GCs). The current study aims to investigate the impact of the biphasic action of the chronic stress response (CSR) induced by the electrical stimulation of the bed nucleus of the stria terminalis (BST) effects on muscle atrophy and aerobic energy metabolism in soleus (SOL) and extensor digitorum longus (EDL) muscles. (2) Male Wistar rats (n = 17) were used. The rats were divided randomly into three groups: the BST two weeks (ST2), four weeks (ST4), and the sham (SHM) electrically stimulated group. The plasma corticosterone (CORT) and irisin concentration were measured. Glucocorticoid and mineralocorticoid receptors (GR and MR), 11β-hydroxysteroid dehydrogenase type 1 and 2 (HSD11B1 and HSD11B2), atrogin-1, and insulin-like growth factor-1 (IGF-1) level were determined in SOL and EDL muscles. Citrate synthase (CS) activity was measured in both muscles. (3) We found elevated plasma concentration of CORT and irisin, raised the level of GR in SOL muscle, and the higher level of MR in both muscles in the ST4 group. The level of HSD11B1 was also higher in the ST4 group compared to the SHM group. Moreover, we observed increased activity of CS in SOL. (4) We suggest that biphasic action of the glucocorticoid induced by the CSR occurs and causes dysregulation of proteins involved in muscle atrophy and aerobic energy metabolism. Our findings potentially contribute to a better understanding of the mechanisms by which GCs and the CSR may regulate muscle atrophy and energy preservation of the red muscle.

Highlights

Stress is one of the most alarming health problems in the modern world
We demonstrated on the same experimental model that rats’ plasma CORT level after the bed nucleus of the stria terminalis (BST) stimulation significantly increased in the four weeks stimulated group (ST4) group as compared with the two weeks stimulated (ST2) and sham-stimulated (SHM) groups [17]
While the different effects of CORT on mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are undoubtedly crucial for various functions, the regulation of mitochondria function by GCs provides new insights to explain the biphasic effects of GCs in muscles function

Summary

Introduction

Stress is one of the most alarming health problems in the modern world. This explains a pressing need for explorations into the biological mechanisms and pathways linking stress and health. It is well documented that the chronic stress response (CSR) leads to extremely negative consequences and is linked to many disease states, affecting the health of many populations. Stress-induced disturbances occur through multiple biochemical and signaling pathways. The major involvement in this process is assigned to the pathways that determine system response to stress through the release of glucocorticoids (GCs) [1,2]. We propose the electric stimulation of the bed nucleus of the stria terminalis (BST) as the model that mimics unconscious stress in rats. The excess high level of GCs occurs in several pathologic conditions such as diabetes, starvation, cancer, burn injuries, and depression, as well as after long-term medical treatment of synthesized GCs [5]

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