EFFECTS OF ANTIMITOTIC DRUGS ON CNS REGENERATION

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The object of the proposed research is to investigate the possibility that reactive non-neuronal cells at the site of a lesion can phagocytose growing axons and their growth cones as they attempt to cross the lesion. The model system used will be the formation and maintenance of apparent presynaptic elements on polylysine coated beads. The apparent presynaptic elements have been shown in cultures of the cerebellum to be neuronal swellings with 40 nm vesicles and with a density acumulated at the membrane in contact with the bead. The apparent presynaptic elements appear to be removed from the beads by non-neuronal cells, but preliminary results show this effect is inhibited by antimitotic drugs which stop non-neuronal cell division. The proposed research will examine the effect of antimitotic drugs on survival of apparent presynaptic elements both in vitro and in vivo. The first studies (I) are in vitro and will examine the effect of different antimitotic drugs on survival of apparent presynaptic elements. In this section additional experiments will use immunocytochemistry to identify the non-neuronal cell types that grow up onto the beads. The second studies (II) are in vivo and will examine the effect of antimitotic drugs on the formation of apparent presynaptic elements in 3-4 day old rats. Preliminary results show that neurons in the cerebellum of 3-4 day old rats do form apparent presynaptic elements on implanted beads. The maintenance of these apparent presynaptic elements and the effect of antimitotic drugs on their survival will be evaluated. The last group (III) of experiments will examine the response of adult cerebellar neurons to polylysine coated beads and the effect of antimitotic drugs on apparent presynaptic element survival. The proposed studies offer a new approach to the understanding of regeneration at the site of lesion. Is the phagocytic response of some non-neuronal cells at the site of CNS lesion possibly involved in the inhibition of axonal regeneration?