Ligand autoradiographical quantification of histamine H3receptor in human dementia with Lewy bodies.
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 H3receptors (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 H3receptor 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 H3correlated with positive psychotic symptoms, in particular delusions and visual hallucinations, but not symptoms associated with depression. Furthermore, no correlation was detected for H3receptor 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.
Department of Biosciences, University of Durham, Durham, UK.
Natasha L
NL
Lethbridge
Department of Biosciences, University of Durham, Durham, UK. Electronic address: paul.chazot@durham.ac.uk.
Paul L
PL
Chazot
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D001345:Autoradiography / Q000379:methods; D001552:Benzazepines / Q000627:therapeutic use; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism; D003704:Dementia / Q000188:drug therapy / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism*; D006212:Hallucinations / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D020961:Lewy Body Disease / Q000188:drug therapy / Q000378:metabolism*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D018100:Receptors, Histamine H3 / Q000378:metabolism*
D001552:Benzazepines; D008024:Ligands; D018100:Receptors, Histamine H3; D009536:Niacinamide; C521312:6-((3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy)-N-methyl-3-pyridinecarboxamide
DLB; Globus pallidus; H(3)R; Histamine; Human; Psychosis