title: Reduced expression of the vesicular acetylcholine transporter and neurotransmitter content affects synaptic vesicle distribution and shape in mouse neuromuscular junction.
abstract: 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.
authors.affiliation: Departamento de Morfologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
authors.forename: Hermann A
authors.initials: HA
authors.lastname: Rodrigues
authors.forename: Matheus de C
authors.initials: Mde C
authors.lastname: Fonseca
authors.forename: Wallace L
authors.initials: WL
authors.lastname: Camargo
authors.forename: Patrícia M A
authors.initials: PM
authors.lastname: Lima
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Martinelli
authors.forename: Lígia A
authors.initials: LA
authors.lastname: Naves
authors.forename: Vânia F
authors.initials: VF
authors.lastname: Prado
authors.forename: Marco A M
authors.initials: MA
authors.lastname: Prado
authors.forename: Cristina
authors.initials: C
authors.lastname: Guatimosim
mesh_terms: D000109:Acetylcholine / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D051379:Mice; D018345:Mice, Knockout; D009045:Motor Endplate / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D000109:Acetylcholine