Ligand autoradiographical quantification of histamine H3 receptor in human dementia with Lewy bodies

Abstract

Dementia with Lewy bodies (DLB) is a serious age-dependent human neurodegenerative disease, with multiple debilitating symptoms, including dementia, psychosis and significant motor deficits, but with little or no effective treatments. This comparative ligand autoradiographical study has quantified histamine H₃ receptors (H₃R) in a series of major cortical and basal ganglia structures in human DLB and Alzheimer's (AD) post-mortem cases using the highly selective radioligand, [³H] GSK189254. In the main, the levels of H₃ receptor were largely preserved in DLB cases when compared with aged-matched controls. However, we provide new evidence showing variable levels in the globus pallidus, and, moreover, raised levels of Pallidum H₃ correlated with positive psychotic symptoms, in particular delusions and visual hallucinations, but not symptoms associated with depression. Furthermore, no correlation was detected for H₃ receptor levels to MMSE or IUPRS symptom severity. This study suggests that H₃R antagonists have scope for treating the psychotic symptomologies in DLB and other human brain disorders.

Keywords: DLB; Globus pallidus; H(3)R; Histamine; Human; Psychosis.