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Role of Sustained Overexpression of Central Nervous System IGF-I in the Age-Dependent Decline of Mouse Excitation-Contraction Coupling

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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 Ca2+ 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 α1-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.

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Acknowledgement

The present study was supported by grants from the National Institutes of Health-National Institute on Aging (AG13934 and AG15820) and the Muscular Dystrophy Association (to O. D.), the National Institute for Human Development (NIHD) (HD008299, to J. A. D.) and the Wake Forest University Claude D. Pepper Older Americans Independence Center (P30-AG21332). We thank Ms. Julie Edelson for editing the manuscript.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Ramón Jiménez Moreno, María Laura Messi, Zhenlin Zheng, Zhong-Min Wang & Osvaldo Delbono

  2. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Ping Ye & Joseph A. D’Ercole

  3. Department of Internal Medicine, Section on Gerontology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Osvaldo Delbono

  4. Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    Osvaldo Delbono

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  1. Ramón Jiménez Moreno
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  2. María Laura Messi
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  3. Zhenlin Zheng
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  4. Zhong-Min Wang
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  7. Osvaldo Delbono
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Correspondence to Osvaldo Delbono.

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Ramón Jiménez Moreno and María Laura Messi contributed equally to this work.

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Moreno, R.J., Messi, M.L., Zheng, Z. et al. Role of Sustained Overexpression of Central Nervous System IGF-I in the Age-Dependent Decline of Mouse Excitation-Contraction Coupling. J Membrane Biol 212, 147–161 (2006). https://doi.org/10.1007/s00232-006-0044-z

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