Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses

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Abstract: Lithium chloride has been widely used as a therapeutic mood stabilizer. Although cumulative evidence suggests that lithium plays modulatory efects on postsynaptic receptors, the underlying mechanism by which lithium regulates synaptic transmission has not been fully elucidated. In this w...

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Autores principales: Zelada, Diego, Barrantes, Francisco José, Henríquez, Juan Pablo
Formato: Artículo
Lenguaje:Inglés
Publicado: Springer Nature 2021
Materias:
LITIO
SINAPSIS NEUROMUSCULAR
ENFERMEDADES NEUROMUSCULARES
RECEPTORES POSTSINAPTICOS
NEUROBIOLOGIA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/12490
https://doi.org/10.1038/s41598-021-96708-7
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-12490
record_format dspace
spelling I33-R139-123456789-124902023-11-22T21:58:25Z Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses Zelada, Diego Barrantes, Francisco José Henríquez, Juan Pablo LITIO SINAPSIS NEUROMUSCULAR ENFERMEDADES NEUROMUSCULARES RECEPTORES POSTSINAPTICOS NEUROBIOLOGIA Abstract: Lithium chloride has been widely used as a therapeutic mood stabilizer. Although cumulative evidence suggests that lithium plays modulatory efects 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 efect of lithium on the stability of postsynaptic nicotinic acetylcholine receptors (nAChRs) in vivo. We found that in normally innervated neuromuscular synapses, lithium chloride signifcantly decreased the turnover of nAChRs by reducing their internalization. A similar response was observed in CHO-K1/A5 cells expressing the adult muscletype 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 fbres. 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 fbres retain β-catenin staining in specifc foci of the synaptic region. Collectively, our data reveal that lithium treatment diferentially afects the stability of postsynaptic receptors in normal and denervated neuromuscular synapses in vivo, thus providing novel insights into the regulatory efects of lithium on synaptic organization and extending its potential therapeutic use in conditions afecting the peripheral nervous system. 2021-10-20T15:24:13Z 2021-10-20T15:24:13Z 2021 Artículo Zelada, D., Barrantes, F.J., Henríquez, J.P. Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses [en línea]. Scientifc Reports. 2021, 11 (17285). Disponible en: https://repositorio.uca.edu.ar/handle/123456789/12490 2045-2322 (en línea) https://repositorio.uca.edu.ar/handle/123456789/12490 https://doi.org/10.1038/s41598-021-96708-7 34446751 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Nature Scientifc Reports 11, Número de artículo 17285, 2021
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic LITIO
SINAPSIS NEUROMUSCULAR
ENFERMEDADES NEUROMUSCULARES
RECEPTORES POSTSINAPTICOS
NEUROBIOLOGIA
spellingShingle LITIO
SINAPSIS NEUROMUSCULAR
ENFERMEDADES NEUROMUSCULARES
RECEPTORES POSTSINAPTICOS
NEUROBIOLOGIA
Zelada, Diego
Barrantes, Francisco José
Henríquez, Juan Pablo
Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses
topic_facet LITIO
SINAPSIS NEUROMUSCULAR
ENFERMEDADES NEUROMUSCULARES
RECEPTORES POSTSINAPTICOS
NEUROBIOLOGIA
description Abstract: Lithium chloride has been widely used as a therapeutic mood stabilizer. Although cumulative evidence suggests that lithium plays modulatory efects 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 efect of lithium on the stability of postsynaptic nicotinic acetylcholine receptors (nAChRs) in vivo. We found that in normally innervated neuromuscular synapses, lithium chloride signifcantly decreased the turnover of nAChRs by reducing their internalization. A similar response was observed in CHO-K1/A5 cells expressing the adult muscletype 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 fbres. 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 fbres retain β-catenin staining in specifc foci of the synaptic region. Collectively, our data reveal that lithium treatment diferentially afects the stability of postsynaptic receptors in normal and denervated neuromuscular synapses in vivo, thus providing novel insights into the regulatory efects of lithium on synaptic organization and extending its potential therapeutic use in conditions afecting the peripheral nervous system.
format Artículo
author Zelada, Diego
Barrantes, Francisco José
Henríquez, Juan Pablo
author_facet Zelada, Diego
Barrantes, Francisco José
Henríquez, Juan Pablo
author_sort Zelada, Diego
title Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses
title_short Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses
title_full Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses
title_fullStr Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses
title_full_unstemmed Lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses
title_sort lithium causes diferential efects on postsynaptic stability in normal and denervated neuromuscular synapses
publisher Springer Nature
publishDate 2021
url https://repositorio.uca.edu.ar/handle/123456789/12490
https://doi.org/10.1038/s41598-021-96708-7
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AT barrantesfranciscojose lithiumcausesdiferentialefectsonpostsynapticstabilityinnormalanddenervatedneuromuscularsynapses
AT henriquezjuanpablo lithiumcausesdiferentialefectsonpostsynapticstabilityinnormalanddenervatedneuromuscularsynapses
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