Selective changes in the levels of nicotinic acetylcholine receptor protein and of corresponding mRNA species in the brains of patients with Parkinson’s disease

Reductions in the number of neuronal nicotinic acetylcholine receptors (nAChRs) have been shown to occur in connection with Parkinson’s disease (PD), but it is still unclear which subtype of this receptor is affected. In the present study we examined various nAChR subtypes employing ligand binding, as well as levels of subunit protein and mRNA in the brains of PD patients and age-matched controls. Binding of [ 3H]epibatidine and levels of α3 mRNA in the caudate nucleus and temporal cortex, but not in the hippocampus were significantly decreased in the PD brain. The level of the α3 protein subunit was significantly reduced in all these brain regions but there was no change in the level of α4. The level of the β2 protein subunit in the temporal cortex and hippocampus and the β2 mRNA in the temporal cortex was lowered. Both the levels of the α7 subunit protein and [ 125I]α-bungarotoxin binding were significantly increased in the temporal cortex of PD patients whereas the α7 mRNA level was unchanged. These findings reveal selective losses of the α3- and β2-containing nAChRs and an increase in the α7 nAChRs that might be related to the pathogenesis of PD.