Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout mice

Abstract

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ColQ Controls Postsynaptic Differentiation at the Neuromuscular Junction

“…In the absence of ColQ as in the absence of AChE, AChR clusters are smaller and fragmented, but in contrast to ColQ mutant mice, the density of AChRs is decreased in adult AChE mutant mice (Xie et al, 2000;Adler et al, 2004). This last phenotype was only evident in mature synapses as neonatal AChE mutant NMJs were normal.…”

Effect of locomotor training on muscle performance in the context of nerve–muscle communication dysfunction

“…We aimed to determine whether LT would ameliorate the soleus muscle performance observed in congenital conditions with altered neuromuscular transmission and neuromuscular fatigability (tetanic fade). [11][12][13] For this purpose, we investigated two murine models with synaptic AChE deficiency: AChE KO and perlecan mutant mice. In a previous study we showed that there was soleus muscle weakness in AChE KO mice (data not shown).…”

“…Absence or reduced level of acetylcholinesterase (AChE) at the neuromuscular junction impairs neuromuscular functioning, because AChE hydrolyzes acetylcholine (ACh) and prevents ACh accumulation with desensitization of ACh receptors. 11 Accordingly, muscles from knockout (KO) AChE mice are unable to maintain force production in response to repetitive nerve stimulation, regardless of frequency. 11,12 Perlecan mutant mice were recently generated by introducing a missense mutation into the Hspg2 gene that encodes perlecan.…”

“…11 Accordingly, muscles from knockout (KO) AChE mice are unable to maintain force production in response to repetitive nerve stimulation, regardless of frequency. 11,12 Perlecan mutant mice were recently generated by introducing a missense mutation into the Hspg2 gene that encodes perlecan. 13 Perlecan mutant mice with an 80% reduction of synaptic AChE are still able to maintain force production but not at lower frequencies (12.5 and 25 HZ) of nerve stimulation.…”

“…Moreover, we studied the effect of LT on soleus muscle contractility of mice that exhibit permanent disturbed neuromuscular junction functioning due to AChE deficiency at the neuromuscular junction. Our third hypothesis was that LT would improve soleus muscle performance of AChE-deficient mice exhibiting severe neuromuscular fatigability, 11,13,14 because reduced muscle activity leads to muscle weakness. 15,16 All these experiments were aimed to provide information on the potential beneficial effect of exercise on muscle weakness observed in the case of neuromuscular diseases affecting nerve-muscle communication.…”