Possible involvement of neuronal nicotinic acetylcholine receptors in compensatory brain mechanisms at early stages of Parkinson’s disease

• Published in: Biochemistry (Moscow). Supplement. Series B, Biomedical chemistry Vol. 11; no. 4; pp. 363 - 370
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-10-2017; Springer Nature B.V
• Subjects: Acetylcholine receptors; Acetylcholine receptors (nicotinic); Animal models; Binding sites; Bioorganic Chemistry; Brain; Bungarotoxin; Chemistry; Chemistry and Materials Science; Dopamine receptors; Epibatidine; Medicinal Chemistry; Movement disorders; mRNA; Neostriatum; Neurodegenerative diseases; Parkinson's disease; Rodents; Substantia nigra; substantia nigra; striatum; nicotinic acetylcholine receptors; dopaminergic neuron; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• ISSN: 1990-7508; 1990-7516
• DOI: 10.1134/S1990750817040035

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 radioligand analysis of nAChR in the striatum and substantia nigra (SN) was performed using the radioactive derivatives of epibatidine, α-conotoxin MII, and α-bungarotoxin. These are selective ligands for different nAChR subtypes. The number of ligand-binding sites changed differently depending on their location in the brain, the stage of the disease and the receptor subtype. In the striatum epibatidine binding decreased by 66% and 70% at the presymptomatic and early symptomatic stages, respectively, while in SN epibatidine binding demonstrated a significant (160%) increase at the presymptomatic stage. The α-conotoxin MII binding to striatal dopaminergic axonal terminals at the presymptomatic stage decreased by 20% and at the symptomatic stage it demonstrated a further decrease. Striatal α-bungarotoxin binding increased at the presymptomatic stage and decreased at the early symptomatic stage. In SN, the level of α-bungarotoxin binding decreased at the presymptomatic stage and remained constant at the symptomatic stage. A significant decrease in the expression of
Chrna4
and
Chrna6
genes encoding α4 and α6 nAChR subunits was observed in SN at the early symptomatic stage, while a 13-fold increase in expression of the
Chrna7
gene encoding the α7 nAChR subunit was detected at the presymptomatic stage. The data obtained on the altered mRNA levels or functional cholinergic receptors suggest possible involvement of nAChR in compensatory mechanisms at early PD stages.