1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences 2. Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia 3. Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia
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.
Keywords: nicotinic acetylcholine receptors, dopaminergic neuron, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, striatum, substantia nigra
Kryukova E.V. et al. Possible involvement of neuronal nicotinic acetylcholine receptors in compensatory brain mechanisms at early stages of Parkinson's disease // Biomeditsinskaya khimiya. - 2017. - V. 63. -N 3. - P. 241-247.
Kryukova E.V. et al., "Possible involvement of neuronal nicotinic acetylcholine receptors in compensatory brain mechanisms at early stages of Parkinson's disease." Biomeditsinskaya khimiya 63.3 (2017): 241-247.
Kryukova, E. V., Shelukhina, I. V., Kolacheva, A. A., Alieva, A. Kh., Shadrina, M. I., Slominsky, P. A., Kasheverov, I. E., Utkin, Y. N., Ugrumov, M. V., Tsetlin, V. I. (2017). Possible involvement of neuronal nicotinic acetylcholine receptors in compensatory brain mechanisms at early stages of Parkinson's disease. Biomeditsinskaya khimiya, 63(3), 241-247.