The trophic requirements of mature motoneurons

Mature motoneurons interact with many cell types, including skeletal muscle fibres, Schwann cells, glia and various neurons. Each of these cell 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 ability of various growth factors to support motoneurons in the absence of muscle fibres, Schwann cells or long-axon synaptic input has been studied using in vivo models. However, these studies do not define the total needs of motoneurons, as local spinal influences have not been removed. In this paper, the total trophic requirement of mature motoneurons was assessed by culturing them at a low cell density, in the absence of all other cell types. Under these conditions, mature motoneurons die by apoptosis within 24 h, which is equivalent to the rate at which immature motoneurons die in vitro. This is consistent with the emerging view that mature cells are primed for apoptosis. Nine putative trophic factors (BDNF, CNTF, FGF2, GDNF, IGF I, IGF II, NT3, NT4, TGF-beta2), 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 axotomy or avulsion. The survival of mature motoneurons may therefore be dependent on a combination of growth factors, with at least one of the factors being distinct from the above mentioned factors.