title: Role of sustained overexpression of central nervous system IGF-I in the age-dependent decline of mouse excitation-contraction coupling.
abstract: We investigated the effects of exclusive and sustained transgenic overexpression of insulin-like growth factor (IGF)-I in the central nervous system (CNS) on the age-dependent decline in muscle strength, excitation-contraction coupling, muscle innervation and neuromuscular junction postterminal architecture. We found that (1) transgenic IGF-I overexpression in the CNS does not modify the decline in extensor digitorum longus (EDL) and soleus muscle weight with aging and (2) strength significantly decreases in transgenic (Tg) compared to wild-type mice. The latter finding is consistent with (3) the decreased absolute and specific force measured in the EDL muscle in vitro and (4) the decreased charge movement and peak intracellular Ca(2+) mobilization in individual muscle fibers from old IGF-I Tg mice compared to young wild-type mice, which also is associated with (5) decreased dihydropyridine receptor alpha(1)-subunit expression in old compared to young IGF-I Tg mice. (6) Tg IGF-I prevents a change in muscle fiber type that is associated with (7) improved muscle innervation and postterminal neuromuscular structure. (8) IGF-I is expressed extensively across the spinal cord gray matter and the lateral motor column. Our results raise questions about the timing and cell location of CNS IGF-I overexpression necessary to prevent or to ameliorate age-dependent alterations in the structure and function of skeletal muscle.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: Ramón Jiménez
authors.initials: RJ
authors.lastname: Moreno
authors.forename: María Laura
authors.initials: ML
authors.lastname: Messi
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Zheng
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
authors.forename: Joseph A
authors.initials: JA
authors.lastname: D'Ercole
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Delbono
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology / Q000502:physiology; D000818:Animals; D020013:Calcium Signaling; D002490:Central Nervous System / Q000378:metabolism*; D004594:Electrophysiology; D015870:Gene Expression; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008959:Models, Neurological; D009119:Muscle Contraction / Q000235:genetics* / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D053580:Muscle Strength / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology / Q000648:ultrastructure; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D007334:Insulin-Like Growth Factor I