Nerve growth factor selectively prevents excitotoxin induced degeneration of striatal cholinergic neurones

Selective neuronal death is a prominent feature of human neurodegenerative disease both of genetic and idiopathic origin. Huntington's disease is characterised by the selective degeneration of striatal projection neurones, with the relative preservation of a variety of interneurones. The ability of the endogenous excitotoxin, quinolinic acid, to produce a pattern of selective neuronal cell death was investigated using immunocytochemical and histochemical techniques. We find that the large striatal, cholinergic interneurones are relatively spared, and that this sparing can be enhanced by the co-administration of the neurotrophin, nerve growth factor (NGF). Further, a single co-injection of NGF will selectively prevent both the cell death and morphological changes that occur within cholinergic cells when assessed 2 weeks later. These results suggest that an interaction between growth factors and excitotoxins can dramatically modify patterns of selective neuronal death.