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Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction

In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KD(HOM)) with 70% reduction in the expression of VAChT to investiga...

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Autores principales: Rodrigues, Hermann A., Fonseca, Matheus de C., Camargo, Wallace L., Lima, Patrícia M. A., Martinelli, Patrícia M., Naves, Lígia A., Prado, Vânia F., Prado, Marco A. M., Guatimosim, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832638/
https://www.ncbi.nlm.nih.gov/pubmed/24260111
http://dx.doi.org/10.1371/journal.pone.0078342
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author Rodrigues, Hermann A.
Fonseca, Matheus de C.
Camargo, Wallace L.
Lima, Patrícia M. A.
Martinelli, Patrícia M.
Naves, Lígia A.
Prado, Vânia F.
Prado, Marco A. M.
Guatimosim, Cristina
author_facet Rodrigues, Hermann A.
Fonseca, Matheus de C.
Camargo, Wallace L.
Lima, Patrícia M. A.
Martinelli, Patrícia M.
Naves, Lígia A.
Prado, Vânia F.
Prado, Marco A. M.
Guatimosim, Cristina
author_sort Rodrigues, Hermann A.
collection PubMed
description In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KD(HOM)) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KD(HOM) mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1–43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KD(HOM) neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KD(HOM) exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape.
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spelling pubmed-38326382013-11-20 Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction Rodrigues, Hermann A. Fonseca, Matheus de C. Camargo, Wallace L. Lima, Patrícia M. A. Martinelli, Patrícia M. Naves, Lígia A. Prado, Vânia F. Prado, Marco A. M. Guatimosim, Cristina PLoS One Research Article In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KD(HOM)) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KD(HOM) mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1–43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KD(HOM) neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KD(HOM) exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape. Public Library of Science 2013-11-08 /pmc/articles/PMC3832638/ /pubmed/24260111 http://dx.doi.org/10.1371/journal.pone.0078342 Text en © 2013 Rodrigues et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rodrigues, Hermann A.
Fonseca, Matheus de C.
Camargo, Wallace L.
Lima, Patrícia M. A.
Martinelli, Patrícia M.
Naves, Lígia A.
Prado, Vânia F.
Prado, Marco A. M.
Guatimosim, Cristina
Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction
title Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction
title_full Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction
title_fullStr Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction
title_full_unstemmed Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction
title_short Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction
title_sort reduced expression of the vesicular acetylcholine transporter and neurotransmitter content affects synaptic vesicle distribution and shape in mouse neuromuscular junction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832638/
https://www.ncbi.nlm.nih.gov/pubmed/24260111
http://dx.doi.org/10.1371/journal.pone.0078342
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