Journal
NEUROSCIENCE LETTERS
Volume 664, Issue -, Pages 1-6Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2017.11.009
Keywords
Skeletal muscle; Hindlimb suspension; Lipid rafts; Acid sphingomyelinase; Ceramide; Clomipramine
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Funding
- [16-15-10220]
- Russian Science Foundation [16-15-10220] Funding Source: Russian Science Foundation
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Disuse-induced skeletal muscle dysfunction is a serious consequence of long-term spaceflight, numerous diseases and conditions for which treatment possibilities are still strictly limited. We have previously shown that acute hindlimb suspension (HS)-mediated disuse disrupts membrane lipid rafts in the unloaded muscle. Here, we investigated whether pretreatment of rats with the inhibitor of acid sphingomyelinase, clomipramine (1.25 mg/g/day, intramuscularly, for 5 days before HS), is able to hinder the loss in lipid raft integrity in response to 12 h of HS. Clomipramine pretreatment significantly counteracted the decrease in labeling of the plasma membranes with lipid raft markers (fluorescent cholera toxin B subunit and bodipy-GM1-ganglioside) specifically in the junctional regions of the suspended soleus muscle. This was associated with: a) enhancing raft disrupting potential of exogenous sphingomyelinase in the junctional membranes; b) prevention of both ceramide accumulation and cholesterol loss; c) prevention of decline in nicotinic acetylcholine receptor labeling in the unloaded muscle. Our data suggest that sphingomyelinase-mediated raft disturbance serves as one of the earlier events in HS effects.
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