EXPRESSION OF NEUROTROPHINS IN SKELETAL-MUSCLE - QUANTITATIVE COMPARISON AND SIGNIFICANCE FOR MOTONEURON SURVIVAL AND MAINTENANCE OF FUNCTION

Neurotrophins play a crucial role in the regulation of survival and ma intenance of specific functions of various populations of neurons, Bra in-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neuro trophin 4/5 (NT-4) have been shown to support motoneuron survival duri ng embryonic development and, after birth, to protect motoneurons from degeneration after nerve lesion, We have compared the levels of these neurotrophins in skeletal muscle by quantitative Northern blot analys is, both during embryonic development and postnatally, We localized th e sites of expression of these neurotrophins by in situ hybridisation and analysed the expression of trkB in the spinal cord by in situ hybr idisation and immunohistochemistry, NT-3 is most abundantly expressed both during embryonic development and in the postnatal phase, followed by NT-4, The levels of BDNF are very low, in particular after birth, After nerve lesion, NT-3 mRNA essentially remained unchanged, whereas NT-4 mRNA rapidly decreased, The slow increase in BDNF expression seem s to be essentially due to the expression in Schwann cells rather than skeletal muscle, demonstrated by in situ hybridisation, Our data indi cate that motoneurons can receive trophic support from several members of the neurotrophin gene family during the period of naturally occurr ing cell death, Postnatally, the predominant ligand acting via trkB on motoneurons is NT-4, whereas BDNF expression seems to play a role mai nly after nerve lesion. (C) 1995 Wiley-Liss, Inc.