THE TROPHIC REQUIREMENTS OF MATURE MOTONEURONS

Mature motoneurons interact with many cell types, including skeletal m uscle fibres, Schwann cells, glia and various neurons. Each of these c ell types is thought to provide trophic support to motoneurons, but it is not known whether the support provided by one cell type can fully substitute for the absence of a signal from another cell type. The abi lity of various growth factors to support motoneurons in the absence o f muscle fibres, Schwann cells or long-axon synaptic input has been st udied using in vivo models. However, these studies do not define the t otal needs of motoneurons, as local spinal influences have not been re moved. In this paper, the total trophic requirement of mature motoneur ons was assessed by culturing them at a low cell density, in the absen ce of all other cell types. Under these conditions, mature motoneurons die by apoptosis within 24 h, which is equivalent to the rate at whic h immature motoneurons die in vitro. This is consistent with the emerg ing view that mature cells are primed for apoptosis. Nine putative tro phic factors (BDNF, CNTF, FGF2, GDNF, IGF I, IGF II, NT3, NT4, TGF-bet a 2), either alone or in combination, were unable to prevent the rapid death of the cultured motoneurons, even though some of these factors are able to attenuate the affects of less severe injuries such as axot omy or avulsion. The survival of mature motoneurons may therefore be d ependent on a combination of growth factors, with at least one of the factors being distinct from the above mentioned factors. (C) 1998 Else vier Science B.V.