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 alpha3 mRNA in the caudate nucleus and temporal cortex, but not in the hippocampus were significantly decreased in the PD brain. The level of the alpha3 protein subunit was significantly reduced in all these brain regions but there was no change in the level of alpha4. The level of the beta2 protein subunit in the temporal cortex and hippocampus and the beta2 mRNA in the temporal cortex was lowered. Both the levels of the alpha7 subunit protein and [125I]alpha-bungarotoxin binding were significantly increased in the temporal cortex of PD patients whereas the alpha7 mRNA level was unchanged. These findings reveal selective losses of the alpha3- and beta2-containing nAChRs and an increase in the alpha7 nAChRs that might be related to the pathogenesis of PD.
Guan
Zhi-Zhong
ZZ
Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Division of Molecular Neuropharmacology, Huddinge University Hospital, B84, S-141 86 Stockholm, Sweden. zhizhong.guan@neurotec.ki.se
Nordberg
Agneta
A
Mousavi
Malahat
M
Rinne
Juha O
JO
Hellström-Lindahl
Ewa
E
D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014316:Tritium; D064569:alpha7 Nicotinic Acetylcholine Receptor
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D018678:Cholinergic Agents; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists; D011725:Pyridines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014316:Tritium; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C419362:nicotinic receptor alpha3beta2; C082748:epibatidine