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

Exp Neurol. 2000 May;163(1):20-30. doi: 10.1006/exnr.2000.7362.


The central histaminergic system is one of the subcortical aminergic projection systems involved in several regulatory functions. The central dopaminergic and histaminergic systems interact extensively, but little is known about the histaminergic system in diseases affecting the dopaminergic neurons. 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 method. Direct connections between dopaminergic neurones and histaminergic fibers were observed. Histamine in human SN was stored in fibers and varicosities. Sites of histamine formation were examined by l-histidine decarboxylase 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 reticulata (SNr), paranigral nucleus, radix of oculomotor nerve, and parabrachial pigmented nucleus was demonstrated. The density of histaminergic fibers in the 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 than in controls and had enlarged varicosities. An increase of histaminergic innervation may reflect a compensatory event due to deficiency of, e.g., dopamine or a putative fiber growth inhibitory factor. Whether the changes seen in histaminergic fibers in PD are primary or secondary remains to be investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Count
  • Dopamine / metabolism
  • Female
  • Histamine / metabolism*
  • Histidine Decarboxylase / biosynthesis
  • Humans
  • Male
  • Middle Aged
  • Nerve Fibers / enzymology*
  • Nerve Fibers / pathology
  • Neurons / enzymology
  • Neurons / pathology*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology*
  • Reference Values
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology*
  • Tyrosine 3-Monooxygenase / metabolism


  • Histamine
  • Tyrosine 3-Monooxygenase
  • Histidine Decarboxylase
  • Dopamine