Ov. Anichtchik et al., Distribution and modulation of histamine H-3 receptors in basal ganglia and frontal cortex of healthy controls and patients with Parkinson's disease, NEUROBIOL D, 8(4), 2001, pp. 707-716
Parkinson's disease (PD) is a brain degenerative disorder with unknown etio
logy, and specific degeneration of mesencephalic dopaminergic cells is a mo
rphological manifestation of the disease. The central histaminergic system
appears to be activated in PD, since the histaminergic innervation is incre
ased in the substantia nigra. The aim of the present study was to investiga
te the expression and function of histamine H-3 receptors in PD, using rece
ptor mRNA in situ hybridization with oligonucleotide probes, receptor bindi
ng assay with a specific radioactive agonist, and GTP-gamma-[S-35]-binding
assay as a tool to study the activation of the receptor G-protein. H-3 rece
ptor binding sites were detected using N-alpha -methylhistamine autoradiogr
aphy in the basal ganglia and cortex, being most abundant in the substantia
nigra and striatum. In PD substantia nigra we detected an increase of the
receptor binding density. In situ hybridization study of the receptor mRNA
revealed prominent sites of H-3 receptor synthesis in the putamen, cortex,
and globus pallidus, whereas very low mRNA expression was seen in the subst
antia nigra. In the PD pallidum externum, H-3 receptor mRNA expression was
elevated as compared with the normal brains. GTP-gamma-[S-35]-binding assay
did not reveal any significant difference between PD and normal brains, al
though the density values in PD substantia nigra tended to be lower than in
the normal brain, and density values in PD striatum were higher. The dopam
inergic neurons did not express significant amount of H-3 receptor mRNA, su
ggesting that the effects of H-3 receptor-mediated modulation of dopamine r
elease are indirect. Our data indicates modulation of the histamine H-3 rec
eptor in PD at the level of the mRNA expression in the striatum and recepto
r density in the substantia nigra. The receptor activity seems to be unchan
ged or decreased, as revealed by GTP-gamma-[S-35]-binding assay. Modulation
of the histamine H-3 receptor may influence the activity of other neurotra
nsmitter systems, e.g., the GABAergic one, in the substantia nigra. (C) 200
1 Academic Press