期刊
NEUROBIOLOGY OF AGING
卷 33, 期 7, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.10.016
关键词
Caudate; Dopaminergic neurons; Histaminergic system; Parkinson's disease; Putamen; Substantia nigra
资金
- Biothechnology and Biological Sciences Research Council (UK)
- Parkinson's UK
- GlaxoSmithKline (UK)
- COST Action [BM0806]
- China Scholarship Council [2007 3020]
- KNAW-CAS of the China [10CDPO37]
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 (H3R), which was localized immunocytochemically in the large pigmented neurons, was significantly decreased in the SN in PD, while histamine receptor-4 (H4R)-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. (C) 2012 Elsevier Inc. All rights reserved.
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