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Striking Denervation of Neuromuscular Junctions without Lumbar Motoneuron Loss in Geriatric Mouse Muscle

By Ruth Jinfen Chai, Jana Vukovic, Sarah Dunlop, Miranda D. Grounds and Thea Shavlakadze


Reasons for the progressive age-related loss of skeletal muscle mass and function, namely sarcopenia, are complex. Few studies describe sarcopenia in mice, although this species is the mammalian model of choice for genetic intervention and development of pharmaceutical interventions for muscle degeneration. One factor, important to sarcopenia-associated neuromuscular change, is myofibre denervation. Here we describe the morphology of the neuromuscular compartment in young (3 month) compared to geriatric (29 month) old female C57Bl/6J mice. There was no significant difference in the size or number of motoneuron cell bodies at the lumbar level (L1–L5) of the spinal cord at 3 and 29 months. However, in geriatric mice, there was a striking increase (by ∼2.5 fold) in the percentage of fully denervated neuromuscular junctions (NMJs) and associated deterioration of Schwann cells in fast extensor digitorum longus (EDL), but not in slow soleus muscles. There were also distinct changes in myofibre composition of lower limb muscles (tibialis anterior (TA) and soleus) with a shift at 29 months to a faster phenotype in fast TA muscle and to a slower phenotype in slow soleus muscle. Overall, we demonstrate complex changes at the NMJ and muscle levels in geriatric mice that occur despite the maintenance of motoneuron cell bodies in the spinal cord. The challenge is to identify which components of the neuromuscular system are primarily responsible for the marked changes within the NMJ and muscle, in order to selectively target future interventions to reduce sarcopenia

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  1. (1978). A quantitative study of peripheral nerve fibres in the mouse following the administration of drugs. 1. Age changes in untreated CBA mice from 3 to 21 months of age.
  2. (2002). Advances in neurobiology of the neuromuscular junction: Implications for the anesthesiologist.
  3. (1981). Age changes in neuromuscular junction morphology and acetylcholine receptor distribution on rat skeletal muscle fibres.
  4. (2011). Age-associated alterations of the neuromuscular junction.
  5. (1998). Age-associated Changes in the innervation of muscle fibers and changes in the mechanical properties of motor units.
  6. (1990). Age-related changes in the neuromuscular junctions in the human posterior cricoarytenoid muscles: A quantitative study.
  7. (2011). Age-related loss of muscle fibres is highly variable amongst mouse skeletal muscles. Biogerontology.
  8. (1990). Ageing alters the myosin heavy chain composition of single fibres from human skeletal muscle.
  9. (2000). Aging of skeletal muscle: a 12-yr longitudinal study.
  10. (2010). Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise.
  11. (2010). Delayed but excellent myogenic stem cell response of regenerating geriatric skeletal muscles in mice.
  12. (1998). Epidemiology of sarcopenia among the elderly in New Mexico.
  13. (2005). Extension and magnitude of denervation in skeletal muscle from ageing mice.
  14. (2007). Factors contributing to neuromuscular impairment and sarcopenia during aging.
  15. (2010). Facts, noise and wishful thinking: muscle protein turnover in aging and human disuse atrophy.
  16. (1992). Fiber-type proportions in mammalian soleus muscle during postnatal development.
  17. (2003). Glial cells and ceurotransmission: an inclusive view of synaptic function.
  18. (2011). How we define the life history phases of mice; how they compare with humans.
  19. (2008). Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis.
  20. (2010). Increased superoxide in vivo accelerates age-associated muscle atrophy through Denervation and Sarcopenia
  21. (2005). Insulin-like growth factor I slows the rate of denervation induced skeletal muscle atrophy.
  22. (1998). Lumbar motor neuron size and number is affected by age in male F344 rats.
  23. (1996). Methods for determining numbers of cells and synapses: A case for more uniform standards of review.
  24. (2008). Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training.
  25. (2006). Morphological changes and selective loss of motoneurons in the lumbar part of the spinal cord in a rat model of familial amyotrophic lateral sclerosis (fALS).
  26. (1990). Morphological changes in the human end plate with age.
  27. (1982). Morphology and enzymatic capacity in arm and leg muscles in 78–81 year old men and women.
  28. (1979). Morphology and physiology of skeletal muscle in aging rodents.
  29. (1989). Morphometric Alteration of Rat Myelinated Fibers with Aging.
  30. (1984). Morphometric analysis of human neuromuscular junction in different ages.
  31. (1966). Motor unit in old age.
  32. (1986). Muscle morphology, enzymatic activity, and muscle strength in elderly men: A follow-up study.
  33. (2010). Muscle wasting in aged, sarcopenic rats is associated with enhanced activity of the ubiquitin proteasome pathway.
  34. (2003). MyoD and myogenin protein expression in skeletal muscles of senile rats.
  35. (1988). Neuron numbers and sizes in aging brain: Comparisons of human, monkey, and rodent data.
  36. (2008). Oxidative stress as a therapeutic target during muscle wasting: considering the complex interactions.
  37. (1999). Preservation of Prefrontal Cortical Volume in Behaviorally Characterized Aged Macaque Monkeys.
  38. (2000). Regulation of neurotrophin signaling in aging sensory and motoneurons.
  39. (2010). Remodeling of the neuromuscular junction precedes sarcopenia related alterations in myofibers.
  40. (1985). Reznick A
  41. (2010). Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure.
  42. (2010). Sarcopenia: European consensus on definition and diagnosis.
  43. (2011). Sarcopenic obesity: satellite cells in the aging muscle.
  44. (1988). Sjo ¨stro ¨m M
  45. (2004). Skeletal muscle fiber types in C57Bl6J mice.
  46. (2006). Skeletal muscle: form and function. USA: Human Kinetics.
  47. (1976). Some observations on the skeletal musculature of aged rats– III. Abnormalities of terminal axons found in motor end-plates.
  48. (2008). Species and strain differences in rodent sciatic nerve anatomy: Implications for studies of neuropathic pain.
  49. (2005). Strategies to reduce age-related skeletal muscle wasting. In:
  50. (2002). Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury.
  51. (2010). Synthesis, modifications, and turnover of proteins during aging.
  52. (2003). The densitometric physical fractionator for counting neuronal populations: application to a mouse model of familial amyotrophic lateral sclerosis.
  53. (1998). The effect of aging on the morphological nerve changes during muscle reinnervation after nerve crush.
  54. (1990). The effect of reinnervation on the distribution of muscle fibre types in the tibialis anterior muscle of the mouse.
  55. (1969). The effect of senility on skeletal muscles in the mouse.
  56. (1981). The localization of motoneurons supplying the hindlim muscles of the mouse.
  57. (1977). The numbers of limb motor neurons in the human lumbosacral cord throughout life.
  58. (1994). The role of the Schwann cell in trophic support and regeneration.
  59. (2001). The spatiotemporal relationship among schwann cells, axons and postsynaptic acetylcholine receptor regions during muscle reinnervation in aged rats. The anatomical record 264:
  60. (2002). The transforming growth factor-betas: multifaceted regulators of the development and maintenance of skeletal muscles, motoneurons and Schwann cells.
  61. (2003). Therapeutic Interventions for Age-related Muscle Wasting - Importance of Innervation and Exercise for Preventing Sarcopenia.
  62. (1989). Three myosin heavy chain isoforms in type 2 skeletal muscle fibres.
  63. (1982). Ultrastructural studies of young and old mouse neuromuscular junctions.
  64. (1991). Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator.
  65. (2006). Widespread loss of neuronal populations in the spinal ventral horn in sporadic motor neuron disease. A morphometric study.

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