Characterization of histamine H-3 receptors in Alzheimer's Disease brain and amyloid over-expressing TASTPM mice

Abstract

Background and purpose: Histamine H receptor antagonists are currently being evaluated for their potential use in a number of central nervous system disorders including Alzheimer's Disease (AD). To date, little is known about the state of H receptors in AD. Experimental approach: In the present study we used the radiolabeled H receptor antagonist [ H]GSKI 89254 to investigate H receptor binding in the amyloid over-expressing double mutant APPswe x PSI.MI46V (TASTPM) transgenic mouse model of AD and In post-mortem human AD brain samples. Key results: No significant differences in specific H receptor binding were observed between wild type and TASTPM mice in the cortex, hippocampus or hypothalamus. Specific [ H]GSK1 89254 binding was detected in sections of human medial frontal cortex from AD brains of varying disease severity (Braak stages I-VI). With more quantitative analysis In a larger cohort, we observed that H3 receptor densities were not significantly different between AD and age-matched control brains in both frontal and temporal cortical regions. However, within the AD group, [ H]GSK1 89254 binding density in frontal cortex was higher in individuals with more severe dementia prior to death. Conclusions and implications: The maintenance of H receptor integrity observed in the various stages of AD in this study is important, given the potential use of H antagonists as a novel therapeutic approach for the symptomatic treatment of AD. © 2009 The British Pharmacological Society All rights reserved.