Immune lesions of noradrenergic neurones in rat central nervous system produced by antibodies to dopamine-β-hydroxylase

Abstract

THE development of antibodies against several neurotransmitter synthesising enzymes has facilitated immunohistochemical identification of specific neurones in the nervous system^1,2. The availability of these antibodies has also raised the possibility of producing immune lesions of the neurones in situations where the antibody has access to its antigen in vivo. In the case of synaptic vesicle antigens, the vesicle membrane becomes incorporated into the nerve terminal membrane during release of transmitter by exocytosis^3–5. Dopamine-β-hydroxylase (DBH), the enzyme that synthesises noradrenaline, is located in the membrane of noradrenergic synaptic vesicles and would become exposed to antibodies in the extracellular space during nerve activity⁶. Binding of injected DBH antibodies has been demonstrated both histochemically and biochemically in sympathetic nerves^7–9. Antibodies to DBH cause degeneration of noradrenergic nerve terminals in several guinea pig tissues when injected intravenously^10,11; this form of immunosympathectomy seems to be a complement-mediated reaction¹². We report here that injection of anti-DBH serum and complement into the cerebrospinal fluid (CSF) of rats produces degeneration of noradrenergic nerve fibres in the central nervous system.