NERVE GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR PROTECT CHOLINERGIC NEURONS AGAINST QUINOLINIC ACID EXCITOTOXICITY IN RAT NEOSTRIATUM

In the present work we have characterized a possible mechanism leading to the early survival of neostriatal cholinergic neurons after quinol inic acid injection. Different doses of quinolinic acid were injected in rat neostriatum and two different parameters were analysed 7 days a fter the lesion: choline acetyltransferase (ChAT) activity and nerve g rowth factor (NGF) levels. We have observed that ChAT activity decreas ed (until 68 nmol quinolinic acid) and NGF levels increased (until 34 nmol quinolinic acid) in a dose-dependent manner. In order to characte rize the time-course of the lesion on NGF levels and ChAT activity, an d the possible protective effect of NGF and basic fibroblast growth fa ctor (bFGF) on cholinergic neurons, we have used the quinolinic acid d ose (68 nmol) at which the first decrease of ChAT activity was observe d. ChAT activity and NGF levels showed different patterns of response to quinolinic acid injection, since the maximal effect was reached at 1 day for ChAT activity and at 2 days for NGF levels. NGF or bFGF simu ltaneously injected with quinolinic acid (68 nmol) completely prevente d the decrease in ChAT activity in a dose-dependent manner but NGF was more effective than bFGF. Furthermore, differences observed in ChAT a ctivity after NGF but not bFGF treatment were correlated with changes in the number of ChAT immunoreactive cells. Finally, we have also obse rved that, although bFGF alone was not able to modify NGF levels, bFGF simultaneously injected with quinolinic acid produced an increase of NGF levels higher than that observed after quinolinic acid injection a lone. Our results show that NGF and bFGF protect striatal cholinergic neurons against quinolinic acid injury, and bFGF is able to potentiate the increase of NGF after the lesion, suggesting a cooperative action between different trophic factors in neuronal protection after excito toxic injury. Thus, administration of trophic factors may be relevant in the prevention and treatment of neurodegenerative disorders, such a s Huntington's disease.