1. [Possible involvement of neuronal nicotinic acetylcholine receptors in compensatory brain mechanisms at early stages of Parkinson's disease].
- Author
-
Kryukova EV, Shelukhina IV, Kolacheva AA, Alieva AK, Shadrina MI, Slominsky PA, Kasheverov IE, Utkin YN, Ugrumov MV, and Tsetlin VI
- Subjects
- Animals, Asymptomatic Diseases, Binding Sites, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Bungarotoxins pharmacology, Conotoxins pharmacology, Corpus Striatum drug effects, Corpus Striatum physiopathology, Disease Models, Animal, Disease Progression, Gene Expression Regulation, Humans, Ligands, Mice, Nicotinic Agonists pharmacology, Organ Specificity, Parkinson Disease, Secondary metabolism, Parkinson Disease, Secondary physiopathology, Protein Binding, Protein Isoforms genetics, Protein Isoforms metabolism, Pyridines pharmacology, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Nicotinic metabolism, Signal Transduction, Substantia Nigra drug effects, Substantia Nigra physiopathology, alpha7 Nicotinic Acetylcholine Receptor metabolism, Corpus Striatum metabolism, Parkinson Disease, Secondary genetics, Receptors, Nicotinic genetics, Substantia Nigra metabolism, alpha7 Nicotinic Acetylcholine Receptor genetics
- Abstract
A role of nicotinic acetylcholine receptors (nAChR) in the development of Parkinson's disease (PD) has been investigated using two mouse models corresponding to the presymptomatic stage and the early symptomatic stage of PD. Quantitative determination of nAChR in the striatum and substantia nigra (SN) was performed using the radioactive derivatives of epibatidine, -conotoxin MII, and -bungarotoxin as ligands. The number of ligand-binding sites changed differently depending on their location in the brain, the stage of the disease and the receptor subtype. Epibatidine binding decreased in the striatum to 66% and 70% at the presymptomatic and early symptomatic stages, respectively, whereas in SN a 160% increase was registered at the presymptomatic stage. The -conotoxin MII binding on striatal dopaminergic axonal terminals at the presymptomatic stage decreased by 20% and at the symptomatic stage it demonstrated a further decrease. The increase in -bungarotoxin binding at the presymptomatic stage and a decrease at the early symptomatic stage was observed in the striatum. In SN, the level of -bungarotoxin binding decreased at the presymptomatic stage and kept constant at the symptomatic stage. The significant decrease in the expression of Chrna4 and Chrna6 genes encoding 4 and 6 nAChR subunits was observed in SN at the early symptomatic stage, while a 13-fold increase in expression of the Chrna7 gene encoding the 7 nAChR subunit was detected at the presymptomatic stage. The data obtained suggest possible involvement of nAChR in compensatory mechanisms at early PD stages.
- Published
- 2017
- Full Text
- View/download PDF