Eca. Kaal et al., PREVENTION OF APOPTOTIC MOTONEURON DEATH IN-VITRO BY NEUROTROPHINS AND MUSCLE EXTRACT, Neurochemistry international, 31(2), 1997, pp. 193-201
In this study, it is shown that rat motoneurons in culture are highly
dependent on trophic support and die in the absence of such support vi
a active cell death, or apoptosis. This apoptotic death occurs in thei
r 'in vitro' life (within 24 h) and can be partially prevented by trea
ting the cultures with neurotrophic substances. The most effective sup
port comes from an extract prepared from embryonic chick muscle: witho
ut muscle extract, no healthy, neurite-bearing motoneurons are present
, but with 0.3 and 1.2% muscle extract, their numbers increase dose-de
pendently. Neurotrophins, such as brain-derived neurotrophic factor (B
DNF) and neurotrophin-4 (NT-4), cannot replace muscle extract and keep
motoneurons alive on their own, but in the presence of muscle extract
(0.3%) they have a significant effect on survival (increase up to fou
r times, compared to 0.3% muscle extract). At the same time, they prev
ent apoptotic cell death. Selective motoneuron death has been implicat
ed in the neurodegenerative disease amyotrophic lateral sclerosis (ALS
). Despite strong evidence that motoneurons in ALS die via apoptosis,
this has not been shown unequivocally in post mortem material. This st
udy shows that motoneurons are very sensitive to conditions that initi
ate apoptosis, and that cell death can be prevented to a large degree
with relatively low concentrations of neurotrophic factors. In view of
the fact that several patient trials with neurotrophic factors alread
y are underway, studies with motoneurons in culture may prove importan
t in understanding the mechanism of cell death and the efficacy of dru
gs such as neurotrophic factors, but also other types of drug. (C) 199
7 Elsevier Science Ltd.