Pyruvate participation in the low molecular weight trophic activity for central nervous system neurons in glia-conditioned media

Abstract

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 (i) pyruvate is the main trophic ingredient of the glia-conditioned medium, and (ii) 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.