Autoradiographic assay of dopamine D2/D3 receptor density and signal transduction pathway activity in Parkinson\'s disease
Dr. Szabolcs Farkas
6 slide(s) – English – 2011-09-10
Nigrostriatal degeneration in Parkinson’s disease (PD) results in different alterions affecting the dopaminergic system. In the present study we aimed to investigate the realtionship between dopamine D2/D3 receptor density and corresponding intracellular signal transduction route activity using human brain samples.
[3H]raclopride binding receptor autoradiography was applied to reveal receptor densities whereas receptor – G protein coupling was investigated with dopamine stimulated [35S]GTPγS binding functional autoradiography. Nucleus caudate, cingulate and medial frontal gyrus control and PD brain specimens were examined. Receptor densities were quantified as [3H]raclopride concentration in fmol/g tissue whereas stimulated [35S]GTPγS binding was expressed as procentual change related to basal binding.
In comparison with control samples dopamine D2/D3 receptor density showed significant decrease in PD nucleus caudate (24.08 ± 2.06 fmol/g tissue (mean ± SEM); 18.43 ± 2.82 fmol/g tissue, p<0.05, respectively). At the same time dopamine stimulated [35S]GTPγS binding did not differed between the two groups (8.7 ± 4.9% and 9.4 ± 4.1%, respectively). In medial frontal and cingulate gyrus samples notable changes were not observed between control and PD samples regarding to the examined parameters.
Our findings suggest that in nucleus caudate the loss of dopamine receptor density is counterbalanced by increased receptor – G protein coupling in treated PD patients, however, this preserved D2 receptor sensitivity could heighten the risk of diskinesias without the efficient regulation of synaptic dopamine levels. At the same time the dopaminergic system in examined non-striatal regions seemed to be intact, however this hypothesis demands further demonstrations using other striatal and non-striatal brain regions.