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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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832638 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078342 | PLOS |
Behav Brain Res
March 2025
Cellular and Behavioral Neuropharmacology Laboratory, Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo, SP, Brazil. Electronic address:
Basal forebrain cholinergic neurons are pivotal for cholinergic signaling in the neocortex and hippocampal formation, crucially implicated in neurodegenerative diseases like late-onset Alzheimer's disease (LOAD), recognition memory impairments, and decision-making. The acetylcholine transporter (VAChT) is essential for loading acetylcholine into synaptic vesicles. Building on our previous findings showing that Ginkgo biloba extract (EGb) preserves recognition memory, we hypothesized EGb would enhance memory in female mice with varying VAChT reductions.
View Article and Find Full Text PDFLife Sci
July 2022
Department of Bioscience, Federal University of São Paulo, Campus Baixada Santista, Santos, Brazil; Department of Clinical Medicine (LIM-20), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address:
Unlabelled: Lung inflammation is modulated by cholinergic signaling and exercise training protects mice against pulmonary emphysema development; however, whether exercise training engages cholinergic signaling is unknown.
Aims: As cholinergic signaling is directly linked to the vesicular acetylcholine transporter (VAChT) levels, we evaluated whether the effects of aerobic exercise training depend on the VAChT levels in mice with pulmonary emphysema.
Main Methods: Wild-type (WT) and mutant (KD) mice (65-70% of reduction in VAChT levels) were exposed to cigarette smoke (30 min, 2×/day, 5×/week, 12 weeks) and submitted or not to aerobic exercise training on a treadmill (60 min/day, 5×/week, 12 weeks).
Am J Physiol Cell Physiol
April 2022
Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
It is well known that cholinergic hypofunction contributes to cardiac pathology, yet, the mechanisms involved remain unclear. Our previous study has shown that genetically engineered model of cholinergic deficit, the vesicular acetylcholine transporter knockdown homozygous (VAChT KD) mice, exhibit pathological cardiac remodeling and a gradual increase in cardiac mass with aging. Given that an increase in cardiac mass is often caused by adrenergic hyperactivity, we hypothesized that VAChT KD mice might have an increase in cardiac norepinephrine (NE) levels.
View Article and Find Full Text PDFSci Rep
August 2021
Departments of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, Brazil.
Acetylcholine (ACh), the neurotransmitter of the cholinergic system, regulates inflammation in several diseases including pulmonary diseases. ACh is also involved in a non-neuronal mechanism that modulates the innate immune response. Because inflammation and release of pro-inflammatory cytokines are involved in pulmonary emphysema, we hypothesized that vesicular acetylcholine transport protein (VAChT) deficiency, which leads to reduction in ACh release, can modulate lung inflammation in an experimental model of emphysema.
View Article and Find Full Text PDFPathophysiology
September 2016
Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo (USP), São Paulo, Brazil. Electronic address:
Chronic kidney disease (CKD) is associated with several other long-lasting conditions such as diabetes and cardiovascular diseases and it is a significant contributor to mortality worldwide. Obstructive kidney disease is one of the leading causes of CKD in children and may result from a wide variety of pathologic processes. Recent studies have shown that α7 nicotinic acetylcholine receptor (α7 nAChR) activation in the cholinergic anti-inflammatory pathway reduces production of inflammatory mediators and consequently prevents tissue injury and death.
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