INTRASTRIATAL INFUSION OF NERVE GROWTH-FACTOR AFTER QUINOLINIC ACID PREVENTS REDUCTION OF CELLULAR EXPRESSION OF CHOLINE-ACETYLTRANSFERASE MESSENGER-RNA AND TRKA MESSENGER-RNA, BUT NOT GLUTAMATE-DECARBOXYLASE MESSENGER-RNA

Excitotoxic striatal lesions induced by quinolinic acid, a model for H untington's disease, were used to test for neuroprotective actions of nerve growth factor on striatal cholinergic and GABAergic neurons. Exp ressions of the trk A receptor for nerve growth factor, choline acetyl transferase and glutamate decarboxylase were analysed by messenger RNA in situ hybridization in adult rats following quinolinic acid lesion (150 nmol) and daily striatal administration of nerve growth factor (1 mu g) or control protein (cytochrome C) for one week. One week after toxin administration, the numbers of cells expressing trkA or choline acetyltransferase messenger RNAs were decreased when compared with unl esioned animals. Moreover, the surviving cells showed a strong down-re gulation of these messenger RNAs as deduced from grain count analysis of sections processed for emulsion autoradiography. Daily intrastriata l nerve growth factor administration for one week completely prevented the reduction in the number of cells expressing either of the two mar kers. Nerve growth factor treatment increased the cellular expression of choline acetyltransferase messenger RNA three times above control l evels and restored the levels of trkA messenger RNA expression to cont rol levels. In contrast to the protective effects on cholinergic cells , nerve growth factor treatment failed to attenuate the quinolinic aci d-induced decrease in glutamate decarboxylase messenger RNA levels. Op tical density measurements of the entire striatum on autoradiographs o f brain sections from quinolinic acid-lesioned animals revealed a redu ction of the glutamate decarboxylase messenger RNA-specific hybridizat ion signal, which was unaltered by infusion of nerve growth factor or control protein. Our findings strongly suggest that in both the intact and the quinolinic acid-lesioned adult rat striatum, nerve growth fac tor action is confined to trkA-expressing cholinergic neurons. Striata l glutamate decarboxylase messenger RNA-expressing GABAergic neurons w hich degenerate in Huntington's disease are not responsive to nerve gr owth factor.