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Pharmacological assays reveal age-related changes in synaptic transmission at the Caenorhabditis elegans neuromuscular junction that are modified by reduced insulin signalling.
MedLine Citation:
PMID:  23038730     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Frailty is a feature of neuromuscular ageing. Here we provide insight into the relative contribution of pre and postsynaptic dysfunction to neuromuscular ageing using the nematode Caenorhabditis elegans. Assays of C. elegans motility highlight a precipitous decline during ageing. We describe a novel deployment of pharmacological assays of C. elegans neuromuscular function to resolve pre and postsynaptic dysfunction that underpin this decreased motility during ageing. The cholinergic agonist levamisole and the cholinesterase inhibitor aldicarb elicited whole worm contraction and allowed a direct comparison of neuromuscular integrity, from 1 to 16 days old: Measurements could be made from aged worms that were otherwise almost completely immobile. The rapidity and magnitude of the drug-induced contraction provides a measure of neuromuscular signalling whilst the difference between levamisole and aldicarb highlights presynaptic effects. Presynaptic neuromuscular transmission increased between one and five days old in wild-type but not in the insulin/IGF1 receptor mutant daf-2 (e1370). Intriguingly, there was no evidence of a role for insulin-dependent effects in older worms. Notably in 16 day old worms, which were virtually devoid of spontaneous movement, the maximal contraction produced by both drugs was unchanged. Taken together the data support a maturation of presynaptic function and/or upstream elements during early ageing that is lost after genetic reduction of insulin signalling. Furthermore, this experimental approach has demonstrated a counterintuitive phenomenon: In aged worms neuromuscular strength is maintained despite the absence of motility.
Authors:
Ben Mulcahy; Lindy Holden-Dye; Vincent O'Connor
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  The Journal of experimental biology     Volume:  -     ISSN:  1477-9145     ISO Abbreviation:  J. Exp. Biol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0243705     Medline TA:  J Exp Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Southampton, UK.
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