Journal of Neuroscience, Vol 5, 23-28, Copyright © 1985 by Society for Neuroscience
Pyruvate participation in the low molecular weight trophic activity for central nervous system neurons in glia-conditioned media
I Selak, SD Skaper and S Varon
Conditioned media from glial cell cultures contain low molecular weight
agents which can support survival of CNS neurons in the absence of
recognized protein neuronotrophic factors. A similar support is provided to
CNS neurons by selected basal media, and pyruvate is the critical medium
constituent responsible for their trophic competence. Eagle's basal medium,
which contains no pyruvate, acquires pyruvate when conditioned over
astroglial cell cultures. Enzymatic degradation of the pyruvate in the
astroglia-conditioned medium leads to corresponding losses in its low
molecular weight trophic activity for CNS neurons. Quantitative
correlations between pyruvate content and CNS trophic activity demonstrate
that pyruvate is the main trophic ingredient of the glia-conditioned
medium, and other low molecular weight substances, acquired during
conditioning, reduce the pyruvate concentration required for its trophic
effect. The "pyruvate-sparing" substances, as yet unidentified, are not the
serine and Fe3+ which have pyruvate-sparing competence for peripheral,
ciliary ganglionic neurons. These findings, together with previous
observations, propose that prenatal neurons fail to generate or retain
endogenous pyruvate at the levels for their survival-sustaining activities.