Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses
Abstract Lithium chloride has been widely used as a therapeutic mood stabilizer. Although cumulative evidence suggests that lithium plays modulatory effects on postsynaptic receptors, the underlying mechanism by which lithium regulates synaptic transmission has not been fully elucidated. In this wor...
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| Format: | Article |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-96708-7 |
| _version_ | 1818422480222552064 |
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| author | Diego Zelada Francisco J. Barrantes Juan Pablo Henríquez |
| author_facet | Diego Zelada Francisco J. Barrantes Juan Pablo Henríquez |
| author_sort | Diego Zelada |
| collection | DOAJ |
| description | Abstract Lithium chloride has been widely used as a therapeutic mood stabilizer. Although cumulative evidence suggests that lithium plays modulatory effects on postsynaptic receptors, the underlying mechanism by which lithium regulates synaptic transmission has not been fully elucidated. In this work, by using the advantageous neuromuscular synapse, we evaluated the effect of lithium on the stability of postsynaptic nicotinic acetylcholine receptors (nAChRs) in vivo. We found that in normally innervated neuromuscular synapses, lithium chloride significantly decreased the turnover of nAChRs by reducing their internalization. A similar response was observed in CHO-K1/A5 cells expressing the adult muscle-type nAChRs. Strikingly, in denervated neuromuscular synapses, lithium led to enhanced nAChR turnover and density by increasing the incorporation of new nAChRs. Lithium also potentiated the formation of unstable nAChR clusters in non-synaptic regions of denervated muscle fibres. We found that denervation-dependent re-expression of the foetal nAChR γ-subunit was not altered by lithium. However, while denervation inhibits the distribution of β-catenin within endplates, lithium-treated fibres retain β-catenin staining in specific foci of the synaptic region. Collectively, our data reveal that lithium treatment differentially affects the stability of postsynaptic receptors in normal and denervated neuromuscular synapses in vivo, thus providing novel insights into the regulatory effects of lithium on synaptic organization and extending its potential therapeutic use in conditions affecting the peripheral nervous system. |
| first_indexed | 2024-12-14T13:26:55Z |
| format | Article |
| id | doaj.art-9d2ddf998bd94992978f5e5e05e0f70e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:26:55Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
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| spelling | doaj.art-9d2ddf998bd94992978f5e5e05e0f70e2022-12-21T22:59:49ZengNature PortfolioScientific Reports2045-23222021-08-0111111510.1038/s41598-021-96708-7Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapsesDiego Zelada0Francisco J. Barrantes1Juan Pablo Henríquez2Neuromuscular Studies Laboratory (NeSt Lab), Department of Cell Biology, CMA Bio-Bio, Facultad de Ciencias Biológicas, Universidad de ConcepciónPontificia Universidad Católica Argentina (UCA)-Scientific and Technological Research Council of Argentina (CONICET)Neuromuscular Studies Laboratory (NeSt Lab), Department of Cell Biology, CMA Bio-Bio, Facultad de Ciencias Biológicas, Universidad de ConcepciónAbstract Lithium chloride has been widely used as a therapeutic mood stabilizer. Although cumulative evidence suggests that lithium plays modulatory effects on postsynaptic receptors, the underlying mechanism by which lithium regulates synaptic transmission has not been fully elucidated. In this work, by using the advantageous neuromuscular synapse, we evaluated the effect of lithium on the stability of postsynaptic nicotinic acetylcholine receptors (nAChRs) in vivo. We found that in normally innervated neuromuscular synapses, lithium chloride significantly decreased the turnover of nAChRs by reducing their internalization. A similar response was observed in CHO-K1/A5 cells expressing the adult muscle-type nAChRs. Strikingly, in denervated neuromuscular synapses, lithium led to enhanced nAChR turnover and density by increasing the incorporation of new nAChRs. Lithium also potentiated the formation of unstable nAChR clusters in non-synaptic regions of denervated muscle fibres. We found that denervation-dependent re-expression of the foetal nAChR γ-subunit was not altered by lithium. However, while denervation inhibits the distribution of β-catenin within endplates, lithium-treated fibres retain β-catenin staining in specific foci of the synaptic region. Collectively, our data reveal that lithium treatment differentially affects the stability of postsynaptic receptors in normal and denervated neuromuscular synapses in vivo, thus providing novel insights into the regulatory effects of lithium on synaptic organization and extending its potential therapeutic use in conditions affecting the peripheral nervous system.https://doi.org/10.1038/s41598-021-96708-7 |
| spellingShingle | Diego Zelada Francisco J. Barrantes Juan Pablo Henríquez Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses Scientific Reports |
| title | Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses |
| title_full | Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses |
| title_fullStr | Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses |
| title_full_unstemmed | Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses |
| title_short | Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses |
| title_sort | lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses |
| url | https://doi.org/10.1038/s41598-021-96708-7 |
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