An altered histaminergic innervation of the substantia nigra in Parkinson's disease

The central histaminergic system is one of the sub cortical aminergic proje ction systems involved in several regulatory functions. The central dopamin ergic and histaminergic systems interact extensively, but little is known a bout the histaminergic system in diseases affecting the dopaminergic neuron s. The distribution of histaminergic fibers in the substantia nigra (SN) in postmortem brain samples from patients suffering from Parkinson's disease (PD) and normal controls was examined with a specific immunohistochemical m ethod. Direct connections between dopaminergic neurones and histaminergic f ibers were observed. Histamine in human SN was stored in fibers and varicos ities. Sites of histamine formation were examined by L-histidine decarboxyl ase in situ hybridization. In both normal and PD brains HDC mRNA was found only in posterior hypothalamus and not in SN. The presence of histaminergic innervation of the human substantia nigra pars compacta (SNc) and reticula ta (SNr), paranigral nucleus, radix of oculomotor nerve, and parabrachial p igmented nucleus was demonstrated. The density of histaminergic fibers in t he middle portion of SNc and SNr was increased in brains with PD. In PD the morphology of histaminergic fibers was also altered; they were thinner tha n in controls and had enlarged varicosities. An increase of histaminergic i nnervation may reflect a compensatory event due to deficiency of, e.g., dop amine or a putative fiber growth inhibitory factor. Whether the changes see n in histaminergic fibers in PD are primary or secondary remains to be inve stigated. (C) 2000 Academic Press.