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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Diego Zelada, Francisco J. Barrantes, Juan Pablo Henríquez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d2ddf998bd94992978f5e5e05e0f70e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9d2ddf998bd94992978f5e5e05e0f70e
record_format	dspace
spelling	oai:doaj.org-article:9d2ddf998bd94992978f5e5e05e0f70e2021-12-02T16:34:53ZLithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses10.1038/s41598-021-96708-72045-2322https://doaj.org/article/9d2ddf998bd94992978f5e5e05e0f70e2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96708-7https://doaj.org/toc/2045-2322Abstract 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.Diego ZeladaFrancisco J. BarrantesJuan Pablo HenríquezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diego Zelada Francisco J. Barrantes Juan Pablo Henríquez Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses
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.
format	article
author	Diego Zelada Francisco J. Barrantes Juan Pablo Henríquez
author_facet	Diego Zelada Francisco J. Barrantes Juan Pablo Henríquez
author_sort	Diego Zelada
title	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_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_sort	lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9d2ddf998bd94992978f5e5e05e0f70e
work_keys_str_mv	AT diegozelada lithiumcausesdifferentialeffectsonpostsynapticstabilityinnormalanddenervatedneuromuscularsynapses AT franciscojbarrantes lithiumcausesdifferentialeffectsonpostsynapticstabilityinnormalanddenervatedneuromuscularsynapses AT juanpablohenriquez lithiumcausesdifferentialeffectsonpostsynapticstabilityinnormalanddenervatedneuromuscularsynapses
_version_	1718383770381320192

Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses

Ejemplares similares