Alterations in the histaminergic system in the substantia nigra and striatum of Parkinson's patients: a postmortem study

Neurobiol Aging. 2012 Jul;33(7):1488.e1-13. doi: 10.1016/j.neurobiolaging.2011.10.016. Epub 2011 Nov 26.

Abstract

Earlier studies showed neuronal histamine production in the hypothalamic tuberomamillary nucleus to be unchanged in Parkinson's disease (PD), whereas the histamine levels and innervation in the substantia nigra (SN) increased. In the present study we used quantitative polymerase chain reaction (qPCR) to assess the changes in the histaminergic system in the SN, caudate nucleus (CN), and putamen (PU) in 7 PD patients and 7 controls. The messenger RNA (mRNA) expression of the histamine receptor-3 (H(3)R), which was localized immunocytochemically in the large pigmented neurons, was significantly decreased in the SN in PD, while histamine receptor-4 (H(4)R)-mRNA expression showed a significant increase in caudate nucleus and PU. In addition, significantly increased mRNA levels of histamine methyltransferase (HMT), a key enzyme involved in histamine metabolism, were found in the SN and in the PU in PD. Moreover, in the SN, the histamine methyltransferase-mRNA showed a strong negative correlation with PD disease duration. Our observations imply the presence of local changes in the histaminergic system that may contribute to PD pathology, and may thus provide a rationale for possible novel therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Corpus Striatum / metabolism*
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology
  • Female
  • Histamine / genetics
  • Histamine / physiology*
  • Histamine N-Methyltransferase / antagonists & inhibitors
  • Histamine N-Methyltransferase / biosynthesis*
  • Histamine N-Methyltransferase / genetics
  • Humans
  • Male
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Putamen / metabolism
  • Putamen / pathology
  • RNA, Messenger / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / biosynthesis*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, Histamine / biosynthesis*
  • Receptors, Histamine / genetics
  • Receptors, Histamine H3 / biosynthesis*
  • Receptors, Histamine H3 / genetics
  • Receptors, Histamine H4
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology
  • Substantia Nigra / physiology

Substances

  • HRH4 protein, human
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H3
  • Receptors, Histamine H4
  • Histamine
  • Histamine N-Methyltransferase