Abstract

Context and objective: The potential application of histamine H3 receptor antagonists in the treatment of several central nervous system illnesses, such as Alzheimer's disease (AD), is presently being investigated. Little is now understood regarding the condition of H3 receptors in AD. Method of experimentation: In the current work, we examined H3 receptor binding in post-mortem human AD brain tissues and the amyloid over-expressing double mutant APPswe ¥ PSI.MI46V (TASTPM) transgenic mouse model of AD using the radiolabelled H3 receptor antagonist [3H]GSK189254.

Important outcomes: There were no discernible variations in the particular H3 receptor binding in the brain, hippocampus, or hypothalamus between wild type and TASTPM mice. Sections of human medial frontal cortex from AD brains with varied disease severity (Braak stages) showed specific [3H]GSK189254 binding 1-VI). We found that, in both frontal and temporal cortical regions, there was no significant difference in H3 receptor densities between AD and age-matched control brains, after conducting a more thorough quantitative investigation on a larger cohort. In contrast, those in the AD group with more advanced dementia prior to death had increased [3H]GSK189254 binding density in the frontal cortex.

Inferences and conclusions: Given the possible use of H3 antagonists as a novel therapeutic approach for the symptomatic treatment of AD, the preservation of H3 receptor integrity shown throughout the various phases of AD in this study is significant.