ABNORMAL DENDRITIC MATURATION OF NEURONS UNDER THE INFLUENCE OF A TILORONE(R) ANALOG (R-10.874)

Tilorone analogue (R 10.874) has a close affinity to the lysosomal com partment of cells and forms a non degradable carbohydrate-lipid-drug c omplex accumulated within digesting organelles. Resembling biochemical and structural changes are seen in hereditary mucopolysaccharidoses a ccompanied with abnormal dendritogenesis. On the other hand, developme ntal toxicity (TERRY et al. 1992), antiproliferative effects (ALGARRA et al. 1993) and interactions with DNA (GELLER et al. 1985) are genera ted by tilorone. Therefore it should be interesting to know whether th e amphiphilic cationic compound is able to produce an abnormal den-dri togenesis as in storage diseases or an impaired arborisation of dendri tes and what could be the reason for the misdevelopment. We demonstrat e that there was a fetal retardation in the development of dendritic n etwork, even under influence of low dosis of the analogue R 10.874. Th e dendritic dismaturation was concomitant with an increased amount of fatty acids and a slightly disarranged metabolic pathway of gangliosid es. The dendritic arborisation closed the gap of retarded development between intrauterine treated and untreated rats after 7 days of postna tal drug elimination. We suppose that a fetotoxic effect and not the l ysosomopathy is responsible for the reduced dendritic network.