Survival and differentiation of dopaminergic mesencephalic neurons are promoted by dopamine-mediated induction of FGF-2 in striatal astroglial cells

Survival of dopaminergic (DAergic) midbrain neurons during development and after lesioning depends, in part, on the presence of astroglia-derived grow th factors, as, e.g., fibroblast growth factor (FGF)-2. Astrocytes express DA receptors in a brain-region-specific manner. We show here that DA (10(-3 ) to 10(-6) mol/liter) applied continuously for 12 h or as a 10-min pulse s ignificantly upregulates FGF-2 immunoreactivity quantified by Western blot and densitometry in astrocytes cultured from two target areas of DAergic ne urons, striatum and cortex, but not in mesencephalic astroglia. Semiquantit ative competitive RT-PCR confirmed the increase in FGF-2 on the mRNA level. The effects were specific in that glutamate, which can also activate recep tors on astroglial cells, did not influence FGF-2 synthesis. In addition to the DA-mediated increase in FGF-2 synthesis the capability of conditioned medium (CM) from DA-stimulated striatal and cortical astrocytes to promote survival and process formation of cultured rat DAergic neurons was signific antly enhanced. These effects could be fully blocked by preincubation of th e CM with an FGF-2-specific polyclonal antiserum. Our results suggest that DA released from DAergic axon terminals in target regions of DAergic neuron s and astroglial FGF-2 production are interdependent in that DA triggers sy nthesis of FGF-2, which, in turn enhances survival and differentiation of D Aeraic neurons.