Target-derived trophic effect on skeletal muscle innervation in senescent mice.
In the present work, we tested the hypothesis that target-derived insulin-like growth factor-1 (IGF-1) prevents alterations in neuromuscular innervation in aging mammals. To explore this hypothesis, we studied senescent wild-type mice as a model of deficient IGF-1 secretion and signaling and S1S2 transgenic mice as a tool to investigate the role of sustained overexpression of IGF-1 in striated muscle in neuromuscular innervation. The analysis of the nerve terminal in extensor digitorum longus muscles from senescent mice showed that the decrease in the percentage of cholinesterase-stained zones (CSZ) exhibiting nerve terminal branching, number of nerve branches at the CSZ, and nerve branch points was partially or completely reversed by sustained overexpression of IGF-1 in skeletal muscle. Target-derived IGF-1 also prevented age-related decreases in the postterminal alpha-bungarotoxin immunostained area, as well as the reduction in the number and length of postsynaptic folds, and area and density of postsynaptic folds studied with electron microscopy. Overexpression of IGF-1 in skeletal muscle may account for the lack of age-dependent switch in muscle fiber type composition recorded in senescent mice. In summary, the use of the S1S2 IGF-1 transgenic mouse model allowed us to provide morphological evidence for the role of target-derived IGF-1 in spinal cord motor neurons in senescent mice.
Messi
Maria Laura
ML
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Delbono
Osvaldo
O
D000375:Aging; D000818:Animals; D002802:Cholinesterases / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000737:chemistry / Q000648:ultrastructure; D018485:Muscle Fibers, Skeletal / Q000737:chemistry; D018482:Muscle, Skeletal / Q000737:chemistry / Q000294:innervation* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000737:chemistry* / Q000648:ultrastructure; D011950:Receptors, Cholinergic / Q000032:analysis
D011950:Receptors, Cholinergic; D007334:Insulin-Like Growth Factor I; D002802:Cholinesterases