Linked Life Data

15483114

Source:http://linkedlifedata.com/resource/pubmed/id/15483114

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
2004-10-14
pubmed:abstractText
Acetylcholinesterase (AChE) exerts noncatalytic activities on neural cell differentiation, adhesion, and neuritogenesis independently of its catalytic function. The noncatalytic functions of AChE have been attributed to its peripheral anionic site (PAS)-mediated protein-protein interactions. Structurally, AChE is highly homologous to the extracellular domain of neuroligin, a postsynaptic transmembrane molecule that interacts with presynaptic beta-neurexins, thus facilitating synaptic formation and maturation. Potential effects of AChE expression on synaptic transmission, however, remain unknown. Using electrophysiology, immunocytochemistry, and molecular biological approaches, this study investigated the role of AChE in the regulation of synaptic formation and functions. We found that AChE was highly expressed in cultured embryonic hippocampal neurons at early culture days, particularly in dendritic compartments including the growth cone. Subsequently, the expression level of AChE declined, whereas synaptic activity and synaptic proteins progressively increased. Chronic blockade of the PAS of AChE with specific inhibitors selectively impaired glutamatergic functions and excitatory synaptic structures independently of cholinergic activation, while inducing AChE overexpression. Moreover, the PAS blockade-induced glutamatergic impairments were associated with a depressed expression of beta-neurexins and an accumulation of other synaptic proteins, including neuroligins, and were mostly preventable by antisense suppression of AChE expression. Our findings demonstrate that interference with the nonenzymatic features of AChE alters AChE expression, which impairs excitatory synaptic structure and functions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8950-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15483114-Acetylcholinesterase, pubmed-meshheading:15483114-Animals, pubmed-meshheading:15483114-Binding Sites, pubmed-meshheading:15483114-Cells, Cultured, pubmed-meshheading:15483114-Cholinesterase Inhibitors, pubmed-meshheading:15483114-Enzyme Inhibitors, pubmed-meshheading:15483114-Glutamic Acid, pubmed-meshheading:15483114-Growth Cones, pubmed-meshheading:15483114-Hippocampus, pubmed-meshheading:15483114-In Situ Hybridization, pubmed-meshheading:15483114-Ligands, pubmed-meshheading:15483114-Nerve Tissue Proteins, pubmed-meshheading:15483114-Neurons, pubmed-meshheading:15483114-Patch-Clamp Techniques, pubmed-meshheading:15483114-Rats, pubmed-meshheading:15483114-Rats, Sprague-Dawley, pubmed-meshheading:15483114-Receptors, Glutamate, pubmed-meshheading:15483114-Synapses, pubmed-meshheading:15483114-Time Factors
pubmed:year
2004
pubmed:articleTitle
Excessive expression of acetylcholinesterase impairs glutamatergic synaptogenesis in hippocampal neurons.
pubmed:affiliation
Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada M4N 3M5.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't