AXONAL OUTGROWTH AND NEURONAL APOPTOSIS IN CULTURED ADULT-MOUSE DORSAL-ROOT GANGLION PREPARATIONS - EFFECTS OF NEUROTROPHINS, OF INHIBITIONOF NEUROTROPHIN ACTIONS AND OF PRIOR AXOTOMY
A. Edstrom et al., AXONAL OUTGROWTH AND NEURONAL APOPTOSIS IN CULTURED ADULT-MOUSE DORSAL-ROOT GANGLION PREPARATIONS - EFFECTS OF NEUROTROPHINS, OF INHIBITIONOF NEUROTROPHIN ACTIONS AND OF PRIOR AXOTOMY, Neuroscience, 75(4), 1996, pp. 1165-1174
Dorsal root ganglia (L4 and L5) with attached spinal roots and nerve s
tumps were isolated from young adult mice and cultured in a layer of e
xtracellular matrix material (matrigel). Within one day, a large numbe
r of axons grew out from the cut ends of the nerve and the dorsal root
. The average outgrowth length was more than doubled by nerve growth f
actor, which also strongly increased the number of fibres, showing ext
ensive branching. There was also a significant outgrowth stimulation b
y neurotrophin-3, but no observable effect by brain-derived neurotroph
ic factor. In preparations isolated and cultured six days after periph
eral nerve transection in vivo, there was an increase in both the outg
rowth length (about 1.5- to 2-fold) and in the number of axons. Stimul
ation of axonal outgrowth, which concerned outgrowth from both the per
ipheral nerve and the dorsal root, could be further enhanced by the ad
dition of nerve growth factor to the culture. K-252a, a selective inhi
bitor of neurotrophin receptor-associated tyrosine kinase activity, di
d not affect either the normal outgrowth or the increased outgrowth in
pre-axotomized preparations, at a concentration which abolished the s
timulating effects by exogenous nerve growth factor and neurotrophin-3
. Under the culturing conditions used, spontaneous apoptosis occurred,
but none of the neurotrophins tested, nor K-252a, affected the number
of apoptotic neuronal cells analysed by nick-labelling DNA breaks at
the end of a 48-h culturing period. Altogether, the present data sugge
st that for most dorsal root ganglia neurons, signalling through the t
rk receptors does not influence the apoptosis in vitro and is not requ
ired for either the spontaneous axonal outgrowth in matrigel or the in
creased outgrowth which occurs after prior axotomy in vivo. Copyright
(C) 1996 IBRO. Published by Elsevier Science Ltd.