The Effect of Reduced Neuromuscular Activity on Class IIa Histone Deacetylase and Selected Downstream Pathways

Abstract

Introduction: Decreased neuromuscular activity, in terms of different models including hindlimb suspension (HS), can result in muscular atrophy by changing different genes expression. Hdac 4&5 and their downstream pathways are 2 important pathways involved in the preservation of muscle mass. Methods: In the current study, in order to survey the changes of Hdac4&5 and their downstream cascade mRNA expression, Wistar rats were assigned into 2 groups (1) weight bearing (WB) and (2) HS (n=5 in each group). Hindlimb’s rats were suspended for 14 days. After 2 weeks, the rats were sacrificed and the soleus and plantaris muscles were gathered. Thereafter, gene expression was determined using eal-time polymerase chain reaction (PCR) technique. Results: The results showed that 14 days HS decreased muscle mass in both the plantaris and soleus muscles and the latter changes definitely outweighed the former. In addition, the crosssectional area of the muscle fibers of the plantaris and soleus muscles decreased and, with changes in muscle mass, the observed decrease in soleus was higher. Also, the increase in mRNA expression of Hdac4&5, myogenin, and Gadd45a, was observed in both muscles. But the expression of the Dach2 gene was significantly reduced in the plantaris and soleus muscles of the HS group as compared to the WB group. Conclusion: Hdac/Myogenin and Hdac/Dach2/Gadd45a participate in muscular atrophy progression.

Keywords

• Muscular atrophy
• Hindlimb suspension
• Histone Deacetylase