Key result
Hindlimb suspension in mice reduced muscle mass and strength by day 14, with early increases in Atrogin-1 and MuRF1 expression by day 1 and reduced IGF-1 expression by day 3.
Early molecular changes such as increased Atrogin-1 and MuRF1 expression precede maximal muscle mass reduction in hindlimb unloading-induced atrophy.
May flag early atrophy targets in unloading models; leaves open translation to clinical disuse atrophy.
INTRODUCTION: Hindlimb unloading-induced muscle atrophy is often assessed after a homeostatic state is established, thus overlooking the early adaptations that are critical to developing this pattern of atrophy. METHODS: Muscle function and physiology were characterized at 0, 1, 3, 7, and 14 days of hindlimb suspension (HS). RESULTS: Reductions in muscle mass were maximal by Day 14 of HS. Functional strength and isolated muscle strength were reduced. MyHC-I and -IIa expressing fibers were reduced in size by Day 7 in the soleus and by Day 14 in the gastrocnemius (MyHC-I fibers only). Atrogin-1 and MuRF1 expression was increased by Day 1 in both the calf and tibialis anterior while IGF-1 expression was significantly reduced on Day 3. Phosphorylation of Akt was reduced on Day 14. CONCLUSIONS: Insight into these early changes in response to HS improves understanding of the molecular and functional changes that lead to muscle atrophy.
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Hanson et al. (2012) studied Hindlimb unloading-induced muscle atrophy. Hindlimb suspension was evaluated on Muscle function and physiology. Hindlimb suspension in mice reduced muscle mass and strength by day 14, with early increases in Atrogin-1 and MuRF1 expression by day 1 and reduced IGF-1 expression by day 3.