Enviar artigo por via de e-mail Possible involvement of neuronal nicotinic acetylcholine receptors in compensatory brain mechanisms at early stages of Parkinson’s disease
- Autores: Kryukova E.V.1, Shelukhina I.V.1, Kolacheva A.A.2, Alieva A.K.3, Shadrina M.I.3, Slominsky P.A.3, Kasheverov I.E.1, Utkin Y.N.1, Ugrumov M.V.2, Tsetlin V.I.1
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Afiliações:
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
- Koltsov Institute of Developmental Biology
- Institute of Molecular Genetics
- Edição: Volume 11, Nº 4 (2017)
- Páginas: 363-370
- Seção: Article
- URL: https://journals.rcsi.science/1990-7508/article/view/198006
- DOI: https://doi.org/10.1134/S1990750817040035
- ID: 198006
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Resumo
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.
Sobre autores
E. Kryukova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Autor responsável pela correspondência
Email: evkr@mail.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997
I. Shelukhina
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Email: evkr@mail.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997
A. Kolacheva
Koltsov Institute of Developmental Biology
Email: evkr@mail.ru
Rússia, Moscow
A. Alieva
Institute of Molecular Genetics
Email: evkr@mail.ru
Rússia, Moscow
M. Shadrina
Institute of Molecular Genetics
Email: evkr@mail.ru
Rússia, Moscow
P. Slominsky
Institute of Molecular Genetics
Email: evkr@mail.ru
Rússia, Moscow
I. Kasheverov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Email: evkr@mail.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997
Y. Utkin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Email: evkr@mail.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997
M. Ugrumov
Koltsov Institute of Developmental Biology
Email: evkr@mail.ru
Rússia, Moscow
V. Tsetlin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Email: evkr@mail.ru
Rússia, ul. Miklukho-Maklaya 16/10, Moscow, 117997
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