A PARACRINE EFFECT FOR NEURON-DERIVED BDNF IN DEVELOPMENT OF DORSAL-ROOT GANGLIA - STIMULATION OF SCHWANN-CELL MYELIN PROTEIN EXPRESSION BYGLIAL-CELLS

Addition of neurons to cultures of non-neuronal cells derived from qua il embryonic dorsal root ganglia causes a 2.5-fold increase in the pro portion of cells that express the glial marker Schwann cell myelin pro tein (SMP) when compared to cultures devoid of neurons. This effect is mediated by BDNF because incubation with a trkB immunoadhesin that se questers BDNF, but not with trkA or trkC immunoadhesins, abolishes thi s stimulation. This neuronal activity can be mimicked by treatment wit h soluble BDNF that stimulates specifically the conversion of SMP-nega tive glial cells into cells that express this phenotype. That BDNF is the endogenous neuron-derived factor affecting glial development is fu rther supported by the observation that BDNF is extensively expressed in developing sensory neurons of the avian ganglia both in vivo and in vitro, but not by the satellite cells. These results show for the fir st time a paracrine role for neuronal BDNF on differentiation of perip heral glial cells. This effect of BDNF is likely to be mediated by the p75 neurotrophin receptor because: (1) p75 immunoreactive protein is expressed by a subset of satellite cells; (2) neutralization of p75 ab olishes the BDNF-induced stimulation; (3) a treatment of non-neuronal cell cultures with equimolar concentrations of either soluble NGF or N T-3 also affects the proportion of cells that become SMP-positive. Whe reas NGF stimulates the acquisition of this glial antigen to a similar extent as BDNF, NT-3 inhibits its expression, suggesting that distinc t neurotrophins signal differentially through p75. These findings also suggest that the definitive phenotype of peripheral glia is determine d by a balance between positive and inhibitory signals arising in adja cent neurons. (C) 1997 Elsevier Science Ireland Ltd.