We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Characterization of histamine H3 receptors in Alzheimer's Disease brain and amyloid over-expressing TASTPM mice.
- Authors
Medhurst, A. D.; Roberts, J. C.; Lee, J.; Chen, C. P. L.-H.; Brown, S. H.; Roman, S.; Lai, M. K. P.
- Abstract
<bold>Background and Purpose: </bold>Histamine H3 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 H3 receptors in AD.<bold>Experimental Approach: </bold>In the present study we used the radiolabelled H3 receptor antagonist [3H]GSK189254 to investigate H3 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.<bold>Key Results: </bold>No significant differences in specific H3 receptor binding were observed between wild type and TASTPM mice in the cortex, hippocampus or hypothalamus. Specific [3H]GSK189254 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, [3H]GSK189254 binding density in frontal cortex was higher in individuals with more severe dementia prior to death.<bold>Conclusions and Implications: </bold>The maintenance of H3 receptor integrity observed in the various stages of AD in this study is important, given the potential use of H3 antagonists as a novel therapeutic approach for the symptomatic treatment of AD.
- Subjects
HISTAMINE receptors; ALZHEIMER'S disease; INFLAMMATORY mediators; PLACEBOS; HUNTINGTON disease; BRAIN metabolism; BRAIN; RESEARCH; GENETIC mutation; HETEROCYCLIC compounds; ANIMAL experimentation; RESEARCH methodology; CELL receptors; PROTEIN precursors; RADIOGRAPHY; ANTIHISTAMINES; EVALUATION research; MEDICAL cooperation; SEVERITY of illness index; VITAMIN B complex; COMPARATIVE studies; RADIOISOTOPES in medical diagnosis; MICE; CEREBRAL cortex; PHARMACODYNAMICS
- Publication
British Journal of Pharmacology, 2009, Vol 157, Issue 1, p130
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1111/j.1476-5381.2008.00075.x