Abstract
The molecular mechanisms of skeletal muscle atrophy under extended periods of either disuse or microgravity are not yet fully understood. The transition of Homer isoforms may play a key role during neuromuscular junction (NMJ) imbalance/plasticity in space. Here, we investigated the expression pattern of Homer short and long isoforms by gene array, qPCR, biochemistry, and laser confocal microscopy in skeletal muscles from male C57Bl/N6 mice (n = 5) housed for 30 days in space (Bion-flight = BF) compared to muscles from Bion biosatellite on the ground-housed animals (Bion ground = BG) and from standard cage housed animals (Flight control = FC). A comparison study was carried out with muscles of rats subjected to hindlimb unloading (HU). Gene array and qPCR results showed an increase in Homer1a transcripts, the short dominant negative isoform, in soleus (SOL) muscle after 30 days in microgravity, whereas it was only transiently increased after four days of HU. Conversely, Homer2 long-form was downregulated in SOL muscle in both models. Homer immunofluorescence intensity analysis at the NMJ of BF and HU animals showed comparable outcomes in SOL but not in the extensor digitorum longus (EDL) muscle. Reduced Homer crosslinking at the NMJ consequent to increased Homer1a and/or reduced Homer2 may contribute to muscle-type specific atrophy resulting from microgravity and HU disuse suggesting mutual mechanisms.
Highlights
Despite the identification of several molecular players at the neuromuscular junction (NMJ) and their specific signaling pathways and cross-talk, the molecular mechanisms whereby neurophysiological nerve impulses are translated into skeletal muscle transcriptional and mechanical responses during NMJ adaptation and plasticity in different loading, unloading, and microgravity environmental conditions are not yet fully understood
We previously reported that components of the Homer protein family are localized at the NMJ postsynaptic microdomain [16], whose expression is regulated by muscle and nerve activity [16,17]
Given the opportunity to participate in the Bion-M1 tissue-sharing program (2012–2013), we investigated the expression and subcellular localization of Homer isoforms at the NMJ of both postural and non-postural muscles in experimental microgravity conditions
Summary
Despite the identification of several molecular players at the NMJ and their specific signaling pathways and cross-talk, the molecular mechanisms whereby neurophysiological nerve impulses are translated into skeletal muscle transcriptional and mechanical responses during NMJ adaptation and plasticity in different loading, unloading, and microgravity (μg) environmental conditions are not yet fully understood. To further investigate such mechanisms, in the last two decades, the U.S National Aeronautics and Space Administration (NASA) and the European Space Agency (ESA) organized several “Space Animal
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