AU  - Dong, Haiheng
AU  - Xiang, Yun-Yan
AU  - Farchi, Noa
AU  - Ju, William
AU  - Wu, Yaojiong
AU  - Chen, Liwen
AU  - Wang, Yutian
AU  - Hochner, Binyamin
AU  - Yang, Burton
AU  - Soreq, Hermona
AU  - Lu, Wei-Yang
TI  - Excessive Expression of Acetylcholinesterase Impairs Glutamatergic Synaptogenesis in Hippocampal Neurons
PT  - JOURNAL ARTICLE
DP  - 2004 Oct 13 
TA  - The Journal of Neuroscience 
PG  - 8950-8960 
VI  - 24 
IP  - 41 
4099 - http://www.jneurosci.org/content/24/41/8950.abstract 
4100 - http://www.jneurosci.org/content/24/41/8950.full 
SO - J. Neurosci. 2004 Oct 13; 24(41):8950-8960 
AID  - 10.1523/JNEUROSCI.2106-04.2004 [doi] 
AB  - 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 β-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 β-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.