RETINOIC ACID INDUCES BDNF RESPONSIVENESS OF SYMPATHETIC NEURONS BY ALTERATION OF TRK NEUROTROPHIN RECEPTOR EXPRESSION

The expression of high affinity neurotrophin receptors (TrkA, TrkB, an d TrkC) determines the survival response of different populations of n eurons to specific members of the neurotrophin family, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ne urotrophin-3 (NT-3). However, the mechanism which controls the express ion of neurotrophin receptors during neuronal development is largely u nknown. Here we show that the treatment of the cultured sympathetic ne urons from newborn rat superior cervical ganglia (SCG) with retinoic a cid (RA), a derivative of vitamin A, suppressed the expression of trkA mRNA and induced the expression of trkB mRNA. Expression of the funct ional TrkB receptor was confirmed by the emergence of trophic dependen ce of these neurons on BDNF in the absence of NGF. Differential regula tion of trk mRNAs by RA provides a possible model for the establishmen t of neurotrophin dependence of peripheral neurons.