Alterations in the histaminergic system in Alzheimer's disease: a postmortem study

Shan, Ling; Bossers, Koen; Unmehopa, Unga; Bao, Ai-Min; Swaab, Dick F.

doi:10.1016/j.neurobiolaging.2011.12.026

« BackNeurobiology of Aging

Article in Press

Alterations in the histaminergic system in Alzheimer's disease: a postmortem study

Ling Shan
- Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China
- Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands
Koen Bossers
- Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands
Unga Unmehopa
- Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands
Ai-Min Bao
- Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China
- Corresponding author at: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China. Tel: +86 571 88208789; fax: +86 571 88208248
Dick F. Swaab
- Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands

Received 19 July 2011; received in revised form 13 December 2011; accepted 22 December 2011. published online 27 January 2012.
Corrected Proof

Abstract

Histamine is produced by the hypothalamic tuberomamillary nucleus (TMN). We studied its involvement in Alzheimer's disease (AD) by in situ hybridization of histidine decarboxylase (HDC), the key enzyme of histamine production, in 9 AD patients and 9 controls. Additionally, messenger (m) RNA levels of the 4 histamine receptors (H_1–4R) and of the enzyme involved in histamine metabolism, histamine methyltransferase (HMT), were determined by quantitative polymerase chain reaction (qPCR) in the prefrontal cortex (PFC) in the course of AD (n = 49). Moreover, alterations in glia markers were studied. HDC-mRNA levels in the TMN were unchanged in AD, despite of the reduced number of Nissl-stained neurons (p = 0.001). However, a decrease in HDC-mRNA was observed in its medial part (mTMN; p = 0.047). In the course of AD only females had increased prefrontal cortex expression of histamine receptor-3 (H₃R) (p = 0.007) and histamine methyltransferase-mRNA (p = 0.011) and of the glia markers, glial fibrillary acidic protein-mRNA, vimentin-mRNA and proteolipid protein-mRNA. These findings indicate the presence of regional changes in the TMN that are at least partly gender-dependent.

Keywords: Histamine , Alzheimer's disease , Tuberomamillary nucleus , Prefrontal cortex , Histamine receptors , Histamine methyltransferase