Early Alterations in Structural and Functional Properties in the Neuromuscular Junctions of Mutant FUS Mice
Abstract
:1. Introduction
2. Results
2.1. Structural Characterization of NMJs: Analysis of End-Plate Fragmentation and Immunolabeling of Presynaptic Proteins
2.2. Structural Characterization of NMJs: The Changes in Synaptic Membrane Properties at Pre-Onset Stage
2.3. Functional Characterization of NMJs in the FUS Mice: Neurotransmitter Reception and Release under Low Calcium in Extracellular Solution
2.3.1. Spontaneous and Evoked Postsynaptic Responses
2.3.2. Estimation of the Real Synaptic Delay and the Kinetics of Neurotransmitter Release
2.4. Functional Characterization of NMJs in the FUS Mice: Neurotransmitter Reception and Release under Normal External Calcium in Extracellular Solution
2.4.1. Spontaneous and Evoked Neurotransmitter Release
2.4.2. Short-Term Plasticity and the Kinetics of Neurotransmitter Release upon Intense Nerve Stimulation
2.5. Functional Characterization of NMJs in the FUS Mice: Estimation of Synaptic Vesicle Endocytosis
2.6. Functional Characterization of NMJs in the FUS Mice: Intraterminal Ca2+ Dynamics upon Nerve Stimulation at Different Frequencies
3. Discussion
4. Materials and Methods
4.1. Animal Model
4.2. Microelectrode Recordings
4.3. Immunostaining
4.4. Lipid Assays
4.5. Assessment of Synaptic Vesicle Endocytosis
4.6. Calcium Imaging
4.7. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | FUS (6–8 w) | WT (6–8 w) | p-Value | FUS (18–20 w) | WT (18–20 w) | p-Value |
---|---|---|---|---|---|---|
nAChR area | 197 ± 20 µm | 205 ± 46 µm | 0.835 | 145 ± 29 µm | 189 ± 25 µm | 0.038 * |
Synapsin 1 area | 97 ± 24 µm | 86 ± 30 µm | 0.403 | 68 ± 17 µm | 83 ± 20 µm | 0.403 |
SNAP-25 area | 80 ± 31 µm | 84 ± 23 µm | 0.531 | 65 ± 28 µm | 72 ± 10 µm | 1 |
Synaptophysin area | 113 ± 12 µm | 118 ± 17 µm | 0.676 | 78 ± 9 µm | 121 ± 38 µm | 0.012 * |
M1 coefficient * | 0.51 ± 0.13 | 0.55 ± 0.13 | 0.362 | 0.35 ± 0.12 | 0.49 ± 0.13 | 0.067 |
M2 coefficient ** | 0.36 ± 0.09 | 0.32 ± 0.70 | 0.208 | 0.22 ± 0.08 | 0.32 ± 0.06 | 0.024 * |
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Mukhamedyarov, M.A.; Khabibrakhmanov, A.N.; Khuzakhmetova, V.F.; Giniatullin, A.R.; Zakirjanova, G.F.; Zhilyakov, N.V.; Mukhutdinova, K.A.; Samigullin, D.V.; Grigoryev, P.N.; Zakharov, A.V.; et al. Early Alterations in Structural and Functional Properties in the Neuromuscular Junctions of Mutant FUS Mice. Int. J. Mol. Sci. 2023, 24, 9022. https://doi.org/10.3390/ijms24109022
Mukhamedyarov MA, Khabibrakhmanov AN, Khuzakhmetova VF, Giniatullin AR, Zakirjanova GF, Zhilyakov NV, Mukhutdinova KA, Samigullin DV, Grigoryev PN, Zakharov AV, et al. Early Alterations in Structural and Functional Properties in the Neuromuscular Junctions of Mutant FUS Mice. International Journal of Molecular Sciences. 2023; 24(10):9022. https://doi.org/10.3390/ijms24109022
Chicago/Turabian StyleMukhamedyarov, Marat A., Aydar N. Khabibrakhmanov, Venera F. Khuzakhmetova, Arthur R. Giniatullin, Guzalia F. Zakirjanova, Nikita V. Zhilyakov, Kamilla A. Mukhutdinova, Dmitry V. Samigullin, Pavel N. Grigoryev, Andrey V. Zakharov, and et al. 2023. "Early Alterations in Structural and Functional Properties in the Neuromuscular Junctions of Mutant FUS Mice" International Journal of Molecular Sciences 24, no. 10: 9022. https://doi.org/10.3390/ijms24109022