IN-VITRO ASSESSMENT OF NEUROTROPHIC ACTIVITY FROM THE STRIATUM OF AGING RATS

Neurotrophic factors are produced in the striatum following trauma and have a demonstrable effect on in vitro bioassays and on in vivo graft survival. We have previously measured the in vitro effect of these fa ctors following trauma to the striatum of young rats. However, the eff ect of age on this neurotrophic response has not been evaluated. In th is study we report on the in vitro effects of extracts (obtained from gelfoam) removed from striatal cavities 7 days following trauma, Gelfo am extract from aged rats (18-24 months) had a reduced neurite-promoti ng response in dorsal root ganglia (DRG) and SH-SY5Y (a dopamine-produ cing neuroblastoma cell line) assays, compared to gelfoam from young r ats (2-3 months). In contrast, extracts from both young and old rats s howed significant neuroprotection of SH-SY5Y cells from the dopaminerg ic neurotoxins N-methy-4phenylpyridinium ion (MPP +) and 6-hydroxydopa mine (6-OHDA). The results suggest that the striatum of aged individua ls may have (1) a diminished capacity for neurite promotion and/or (2) that neurite outgrowth and neuroprotection may be influenced by diffe rent factors or different levels of the same factors. The direct impli cation is that aged animals would be the most appropriate models to st udy experimental therapies for Parkinson's disease.