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

• Autores: Zelada, Diego; Barrantes, Francisco José; Henríquez, Juan Pablo
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Scientifc Reports 11, Número de artículo 17285, 2021
• Materia: LITIO; SINAPSIS NEUROMUSCULAR; ENFERMEDADES NEUROMUSCULARES; RECEPTORES POSTSINAPTICOS; NEUROBIOLOGIA
• Institución: Pontificia Universidad Católica Argentina

Fil: Zelada, Diego. Neuromuscular Studies Laboratory; Estados Unidos
Fil: Zelada, Diego. Universidad de Concepción. Facultad de Ciencias Biológicas. Centro de Microscopía Avanzada; Argentina
Fil: Zelada, Diego. Pontificia Universidad Católica Argentina; Argentina
Fil: Barrantes, Francisco José. Pontificia Universidad Católica Argentina; Argentina
Fil: Barrantes, Francisco José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Henríquez, Juan Pablo. Neuromuscular Studies Laboratory; Estados Unidos
Fil: Henríquez, Juan Pablo. Universidad de Concepción. Facultad de Ciencias Biológicas. Centro de Microscopía Avanzada; Argentina
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.