Dong_2004_J.Neurosci_24_8950

Reference

Title : Excessive expression of acetylcholinesterase impairs glutamatergic synaptogenesis in hippocampal neurons - Dong_2004_J.Neurosci_24_8950
Author(s) : Dong H , Xiang YY , Farchi N , Ju W , Wu Y , Chen L , Wang Y , Hochner B , Yang B , Soreq H , Lu WY
Ref : Journal of Neuroscience , 24 :8950 , 2004
Abstract :

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.

PubMedSearch : Dong_2004_J.Neurosci_24_8950
PubMedID: 15483114

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Family Neuroligin

Citations formats

Dong H, Xiang YY, Farchi N, Ju W, Wu Y, Chen L, Wang Y, Hochner B, Yang B, Soreq H, Lu WY (2004)
Excessive expression of acetylcholinesterase impairs glutamatergic synaptogenesis in hippocampal neurons
Journal of Neuroscience 24 :8950

Dong H, Xiang YY, Farchi N, Ju W, Wu Y, Chen L, Wang Y, Hochner B, Yang B, Soreq H, Lu WY (2004)
Journal of Neuroscience 24 :8950