Analysis of neurotrophic effects of hepatocyte growth factor in the adult hypoglossal nerve axotomy model

Analysis of neurotrophic effects of hepatocyte growth factor in the adult hypoglossal nerve... Recent studies have shown that hepatocyte growth factor (HGF) promotes the survival of embryonic motor neurons. However, it remains unclear whether HGF has trophic effects on mature motor neurons. In the present study, we examined the effects of HGF on adult motoneurons using the hypoglossal nerve transection model. In adult rats, neurons in the hypoglossal nucleus show a dramatic loss of choline acetyltransferase (ChAT) protein and mRNA after the axotomy. This reduction of ChAT was markedly prevented when HGF was administered continuously at the cut end of the nerve using an osmotic pump. The HGF receptor, c‐met, protein and mRNA, which were faintly expressed in hypoglossal neurons under normal conditions, gradually increased and reached maximal levels 2 weeks after the axotomy. Administration of HGF reduced this c‐met upregulation almost to normal levels. We also quantified HGF mRNA in the tongue and hypoglossal nucleus. The tongue contained abundant HGF mRNA, whereas the nucleus contained only low levels. Interestingly, the HGF mRNA level in the nucleus did not increase after the axotomy. These findings suggest that HGF is principally produced in the tongue and contributes to maintain ChAT expression in the nucleus. HGF produced in the hypoglossal nucleus alone after disconnection from the tongue may not be sufficient for the maintenance of the motor neuron function. Thus, exogenously applied HGF was effective to prevent the downregulation of ChAT activities. These findings provide a strong rationale for the potential clinical use of HGF for the treatment of motor neuron degenerative disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Analysis of neurotrophic effects of hepatocyte growth factor in the adult hypoglossal nerve axotomy model

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Publisher
Wiley
Copyright
Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1046/j.1460-9568.1999.00832.x
Publisher site
See Article on Publisher Site

Abstract

Recent studies have shown that hepatocyte growth factor (HGF) promotes the survival of embryonic motor neurons. However, it remains unclear whether HGF has trophic effects on mature motor neurons. In the present study, we examined the effects of HGF on adult motoneurons using the hypoglossal nerve transection model. In adult rats, neurons in the hypoglossal nucleus show a dramatic loss of choline acetyltransferase (ChAT) protein and mRNA after the axotomy. This reduction of ChAT was markedly prevented when HGF was administered continuously at the cut end of the nerve using an osmotic pump. The HGF receptor, c‐met, protein and mRNA, which were faintly expressed in hypoglossal neurons under normal conditions, gradually increased and reached maximal levels 2 weeks after the axotomy. Administration of HGF reduced this c‐met upregulation almost to normal levels. We also quantified HGF mRNA in the tongue and hypoglossal nucleus. The tongue contained abundant HGF mRNA, whereas the nucleus contained only low levels. Interestingly, the HGF mRNA level in the nucleus did not increase after the axotomy. These findings suggest that HGF is principally produced in the tongue and contributes to maintain ChAT expression in the nucleus. HGF produced in the hypoglossal nucleus alone after disconnection from the tongue may not be sufficient for the maintenance of the motor neuron function. Thus, exogenously applied HGF was effective to prevent the downregulation of ChAT activities. These findings provide a strong rationale for the potential clinical use of HGF for the treatment of motor neuron degenerative disease.

Journal

European Journal of NeuroscienceWiley

Published: Nov 1, 1999

References

  • Neurotrophic effect of hepatocyte growth factor on central nervous system neurons in vitro
    Hamanoue, Hamanoue; Takemoto, Takemoto; Matsumoto, Matsumoto; Nakamura, Nakamura; Nakajima, Nakajima; Kohsaka, Kohsaka
  • Expression and functional interaction of hepatocyte growth factor‐scatter factor and its receptor c‐met in mammalian brain
    Jung, Jung; Castren, Castren; Odenthal, Odenthal; Vande‐Woude, Vande‐Woude; Ishii, Ishii; Dienes, Dienes; Londholm, Londholm; Schimacher, Schimacher
  • Scatter factor/hepatocyte growth factor and its receptor, the c‐met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development
    Sonnenberg, Sonnenberg; Meyer, Meyer; Weidner, Weidner; Birchmeier, Birchmeier
  • Brain‐derived neurotrophic factor spares choline acetyltransferase mRNA following axotomy of motor neurons in vivo
    Wang, Wang; Salvaterra, Salvaterra; Loera, Loera; Chiu, Chiu

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