DIFFERENTIAL REGULATION OF BDNF AND NT-3 MESSENGER-RNA LEVELS IN PRIMARY CULTURES OF RAT CEREBELLAR NEURONS

Reciprocal developmental patterns of expression for BDNF and NT-3 have been observed in several neuronal types, including cerebellar granule neurons: NT3 mRNA level decreased and BDNF mRNA increased in granule cells concomitantly with their migration and maturation. In the presen t study we analysed cultured cerebellar granule neurons prepared from postnatal rat cerebellum, a model system widely used for studies on th e maturation and survival of these neurons. We show that chronic depol arization, induced by 25 mM K+ in the culture medium, is able to susta in a persistent increase of BDNF expression in cerebellar granule neur ons. It has been suggested that chronic depolarization in vitro mimics the effect of the earliest afferent inputs received by granule cells in vivo: on this basis we suggest that the beginning of neuronal activ ity in differentiated granule neurons may represent one of the signals that trigger the developmental increase in BDNF expression. Interesti ngly, we observed that up-regulation of BDNF expression in vitro is ac companied by a dramatic decrease of NT-3 expression: a differential re gulation that is highly reminiscent of the reciprocal developmental pa tterns of expression observed in vivo for BDNF and NT-3. Another point raised by the present results is the possible role of BDNF, acting in an autocrine or paracrine manner, in the trophic effect of high potas sium concentration. Indeed, repeated additions of BDNF to the culture medium have a trophic effect on cerebellar granule neurons but reprodu ce only partially the survival effect observed with 25 mM K+ condition s, suggesting that the increased expression of BDNF is not the only me chanism responsible for the trophic effects of high potassium. In conc lusion we show the existence of a reciprocal regulation of BDNF and NT -3 expression in cultured cerebellar granule neurons and we propose th at this culture system could represent an in vitro model for the study of the molecular mechanisms underlying the developmental regulation o f these neurotrophins in cerebellum. (C) 1998 Elsevier Science Ltd. Al l rights reserved.