The Effect of Dehydroepiandrosterone Sulfate (DHEAS) on Myotonia: Intracellular Studies

Abstract

Objective In order to find some appropriate medicine to suppress myotonia without decreasing muscle strength experiments were performed on myotonic (mto) mice whose Cl channel does not develop due to stop codon and serves as an animal model of myotonia. In myotonic dystrophy dehydroepiandrosterone is low in the serum and it has been reported that intravenous injections of DHEAS to human cases improves myotonia and activities of daily living.Materials and Methods Three pairs of heterozygote mto mice, SWR/J-Clcn1 adr-mto/+ and ten Wistar rats were used. We performed intracellular recordings of myotonia from mto mice and the drug effects on insertion myotonia were recorded from the hemidiaphragm preparations of mto mice with different concentrations of DHEAS. Isometric twitch tension was recorded from rat hemidiaphragm preparations in Tyrode's solution and the effect of DHEAS on the muscle twitch tension was measured at different concentrations of DHEAS from 100 mg/l to 300 mg/l. The effect of mexiletine on ITT was also measured.Results In mto mice insertion myotonia was recorded as soon as the microeletrode was inserted in the muscle cells. When DHEAS was added to Tyrode's solution, insertion myotonia was suppressed. DHEAS decreased ITT up to 70% of the original value, though mexiletine decreased ITT to 30% of the original value. Therefore, the decrement of the muscle strength in DHEAS solution is much smaller than that of mexiletine.Conclusion Since myotonic dystrophy shows progressive muscle weakness in addition to myotonia, medications like DHEAS are more favorable than the typical Na channel blocker. (Internal Medicine 44: 1247-1251, 2005)

The myotonic dystrophies: diagnosis and management

“…DM1 may be associated with low circulating dehydroepiandrosterone (DHEA) levels 78 79. An initial pilot study suggested that DHEA may improve myotonia and muscle strength in DM1 80.…”

Dehydroepiandrosterone Stimulates Phosphorylation of FoxO1 in Vascular Endothelial Cells via Phosphatidylinositol 3-Kinase- and Protein Kinase A-dependent Signaling Pathways to Regulate ET-1 Synthesis and Secretion

“…This is coupled with age-associated increases in insulin resistance, cardiovascular diseases, neurological disorders, and musculoskeletal frailty (42)(43)(44). Moreover, DHEA has biological actions in cell-based systems and animal models that mimic many of the actions of insulin and other hormones important for metabolic, cardiovascular, and neurological function (19,(45)(46)(47)(48)(49). Taken together, these observations have led to the hypothesis that DHEA supplementation may have beneficial health effects in humans to oppose age-related declines in metabolic, cardiovascular, neurological, and musculoskeletal function (50).…”

Pharmacological treatment for muscle weakness and wasting in myotonic dystrophy

“…It has been implicated in a broad range of biological functions and can be converted to the sex steroid, testosterone. DM1 may be associated with low circulating dehydroepiandrosterone (DHEA) levels (Carter 1985;Nakazora 2005). An initial pilot study suggested that DHEA may improve myotonia and muscle strength in DM1 (Sugino 1998).…”