A SUBPOPULATION OF STRIATAL GABAERGIC NEURONS EXPRESSES THE EPIDERMALGROWTH-FACTOR RECEPTOR

Epidermal growth factor and transforming growth factor alpha are mitog enic polypeptides that act at the epidermal growth factor receptor, a protein tyrosine kinase.(10,16,18,24) Studies have shown that epiderma l growth factor and transforming growth factor alpha support the survi val and promote the differentiation of central nervous system neurons in vitro.(13,21,33) Messenger RNAs for both transforming growth factor alpha and the epidermal growth factor receptor have been identified i n the adult and developing mammalian central nervous system, particula rly within the neostriatum of young animals.(11,15,22,27,28,30) Howeve r, the cell types that synthesize these messenger RNAs in striatum are not well understood. The present study investigates the hypothesis th at epidermal growth factor receptor and transforming growth factor alp ha are synthesized by striatal GABAergic neurons using double-labeling in situ hybridization in the rat, Most neurons within the neostriatum that intensely expressed messenger RNA for the 67,000 mol. wt isoform of glutamate decarboxylase also expressed messenger RNA for the epide rmal growth factor receptor. Scattered striatal cells with neuronal mo rphology were immunoreactive for epidermal growth factor receptor prot ein, indicating that epidermal growth factor receptor messenger RNA ex pressed by striatal neurons is translated, Striatal neurons that expre ssed high levels of the 67,000 mel. wt isoform of glutamate decarboxyl ase messenger RNA did not appear to express transforming growth factor alpha messenger RNA. The present study indicates that epidermal growt h factor receptor is synthesized by subpopulation of GABAergic striata l neurons, supporting the hypothesis that transforming growth factor a lpha and epidermal growth factor act directly upon neurons to produce their neurotrophic effects. These neurons may be GABAergic interneuron s, which have been shown to be relatively resistant to degeneration in Huntington's disease and excitotoxic models of this disease.(6,7,9)