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Journal article

Over-expression of parvalbumin in transgenic mice rescues motoneurons from injury-induced cell death

  • Dekkers, J. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London UK
  • Bayley, P. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London UK
  • Dick, J. R. T. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London UK
  • Schwaller, Beat Institute of Histology, Department of Medicine, University of Fribourg, Switzerland
  • Berchtold, M. W. Department of Molecular Cell Biology, Institute of Molecular Biology, University of Copenhagen, Denmark
  • Greensmith, L. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London UK
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    23.12.2004
Published in:
  • Neuroscience. - 2004, vol. 123(2), no. 459-466
axotomy
calcium-binding proteins
glutamate excitotoxicity
English Following nerve injury in neonatal rats, a large proportion of motoneurons die, possibly as a consequence of an increase in vulnerability to the excitotoxic effects of glutamate. Calcium-dependent glutamate excitotoxicity is thought to play a significant role not only in injury-induced motoneuron death, but also in motoneuron degeneration in diseases such as amyotrophic lateral sclerosis (ALS). Motoneurons are particularly vulnerable to calcium influx following glutamate receptor activation, as they lack a number of calcium binding proteins, such as calbindin-D28k and parvalbumin. Therefore, it is possible that increasing the ability of motoneurons to buffer intracellular calcium may protect them from cell death and prevent the decline in motor function that usually occurs as a consequence of motoneuron loss. In this study we have tested this possibility by examining the effect of neonatal axotomy on motoneuron survival and muscle force production in normal and transgenic mice that over-express parvalbumin in their motoneurons.The sciatic nerve was crushed in one hindlimb of new-born transgenic and wildtype mice. The effect on motoneuron survival was assessed 8 weeks later by retrograde labelling of motoneurons innervating the tibialis anterior muscle. Following nerve injury in wildtype mice, only 20.2% (±2.2, S.E.M.; n=4) of injured motoneurons survive long term compared with 47.2% (±4.4, S.E.M.; n=4) in parvalbumin over-expressing mice. Surprisingly, this dramatic increase in motoneuron survival was not reflected in a significant improvement in muscle function, since 8 weeks after injury there was no improvement in either maximal twitch and tetanic force, or muscle weights.Thus, inducing spinal motoneurons to express parvalbumin protects a large proportion of motoneurons from injury-induced cell death, but this is not sufficient to restore muscle function.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
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https://folia.unifr.ch/unifr/documents/299544
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