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dc.contributor.author
Zelada, Diego
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Barrantes, Francisco Jose
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Henríquez, Juan Pablo
dc.date.available
2022-09-21T17:41:27Z
dc.date.issued
2021-12
dc.identifier.citation
Zelada, Diego; Barrantes, Francisco Jose; Henríquez, Juan Pablo; Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses; Nature Research; Scientific Reports; 11; 1; 12-2021; 1-15
dc.identifier.uri
http://hdl.handle.net/11336/169792
dc.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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Research
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
neuromuscular junction
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lithium
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nicotinic acetylcholine receptor
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synapse stability
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-09-09T17:22:26Z
dc.identifier.eissn
2045-2322
dc.journal.volume
11
dc.journal.number
1
dc.journal.pagination
1-15
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Zelada, Diego. Universidad Católica de la Santísima Concepción; Chile
dc.description.fil
Fil: Barrantes, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina
dc.description.fil
Fil: Henríquez, Juan Pablo. Universidad Católica de la Santísima Concepción; Chile
dc.journal.title
Scientific Reports
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-021-96708-7
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/s41598-021-96708-7
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