Effects of inhibition of glycogen synthase kinase 3p on neuromuscular synaptic transmission in transgenic mice with model of alzheimer's disease
- Authors: Mukhamedyarov M.A1, Grigoryev P.N1, Ushanova E.A2, Zefirov A.L1
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Affiliations:
- Kazan State Medical University
- Kazan (Volga Region) Federal University
- Issue: Vol 15, No 4 (2020)
- Pages: 57-60
- Section: Articles
- URL: https://genescells.ru/2313-1829/article/view/121983
- DOI: https://doi.org/10.23868/202012009
- ID: 121983
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Abstract
Alzheimer's disease is the most common neurodegenera-tive disease. Synaptic dysfunction plays important role in pathogenesis of Alzheimer's disease. Recently, glycogen synthase kinase 3 has been considered as a potential target for therapy of Alzheimer's disease, since the activity of this enzyme, which regulates many cellular and synaptic functions, is impaired in this pathology. In this paper, we studied the effects of inhibition of glycogen synthase kinase 3p on the parameters of the peripheral (neuromuscular) synapse functioning in the Alzheimer's disease model in APP/PS1 transgenic mice. In electrophysiological experiments on the diaphragm of APP/PS1 of mice, application of the glycogen synthase kinase 3p inhibitor AR-A014418 (1 pM) did not cause significant changes in the parameters of spontaneous and evoked neurotransmitter release, as well as in the dynamics of the amplitude of the end-plate potentials during high-frequency stimulation. In fluorescent experiments using the dye FM 1-43, it was found that the application of AR-A014418 (1 pM) does not significantly change the intensity of endocytosis, but causes moderate enhancement of exocytosis of synaptic vesicles during high-frequency stimulation. Enhancement of synaptic vesicle exocytosis due to inhibition of glycogen synthase kinase 3p may alleviate neuromuscular synaptic dysfunction in APP/PS1 mice. The obtained results can be used in studies aimed to development of therapeutic strategies for Alzheimer's disease.
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About the authors
M. A Mukhamedyarov
Kazan State Medical University
P. N Grigoryev
Kazan State Medical University
E. A Ushanova
Kazan (Volga Region) Federal University
A. L Zefirov
Kazan State Medical University
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