GLIA CONDITIONED MEDIUM PROTECTS FETAL-RAT MIDBRAIN NEURONS IN CULTURE FROM L-DOPA TOXICITY

L-DOPA kills dopamine neurones in culture but is the most effective dr ug for the treatment of Parkinson's disease, where it exhibits no clea r toxicity. While glial cells surround and protect neurones in vivo, n eurones are usually cultured in vitro in the absence of glia. We treat ed fetal midbrain rat neurones with L-DOPA, mesencephalic glia conditi oned medium (CM) and L-DOPA + CM. L-DOPA reduced the number of tyrosin e hydroxylase-positive (TH+) cells and [H-3]DA uptake, and increased q uinone levels. L-DOPA + CM restored [H-3]DA uptake and quinone levels to normal, and increased the number of TH+ cells and terminals to 170% of control. CM greatly increased the number of TH+ cells and [H-3]DA uptake. Mesencephalic glia therefore produced soluble factors which ar e neurotrophic for dopamine neurones, and which protect these neurones from the toxic effects of L-DOPA.