Reference Report

Reference
Citation	Kim, W., Lee, D., Choi, J., Kim, A., Han, S., Park, K., Choi, J., Kim, J., Choi, Y., Lee, S.H., Koh, Y.H. (2011). Pharmacogenetic Regulation of Acetylcholinesterase Activity in Drosophila Reveals the Regulatory Mechanisms of AChE Inhibitors in Synaptic Plasticity. Neurochem. Res. 36(5): 879--893. (Export to RIS)
FlyBase ID	FBrf0213378
Publication Type	Research paper
PubMed ID	21305389
PubMed Abstract	We conducted experiments in Drosophila to investigate the consequences of altered acetylcholinesterase (AChE) activity in the nervous system. In ace hypomorphic mutant larvae, the amount of ace mRNA and the activity of AChE both in vivo and in vitro were significantly reduced compared with those of controls. Reduced Ace in Drosophila larvae resulted in significant down-regulation of branch length and the number of boutons in Type 1 glutamatergic neuromuscular junctions (NMJs). These defects in ace hypomorphic mutant larvae were suppressed when Musca domestica AChE was transgenically expressed. Because AChE inhibitors are utilized for medications for Alzheimer's disease, we investigated whether pharmacological inhibition of AChE activity induced any synaptic defects. We found that controls exposed to a sublethal dose of DDVP phenocopied the synaptic structural defects of the ace hypomorphic mutant. These results suggest that down-regulation of AChE activity, regardless of whether it is due to genetic or pharmacological manipulations, results in altered synaptic architecture. Our study suggests that exposure to AChE inhibitors for 6-12 months may induce altered synaptic architectures in human brains with Alzheimer's diseases, similar to those reported here. These changes may underlie or contribute to the loss of efficacy of AChE inhibitors after prolonged treatment.
DOI	10.1007/s11064-011-0418-1
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Secondary IDs
Language of Publication	English
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Publication Type	Journal
Abbreviation	Neurochem. Res.
Title	Neurochemical Research
Publication Year	1976-
ISBN/ISSN	0364-3190
Data from Reference
Aberrations (1)
	Df(3R)Exel6167
Alleles (7)
	Ace^c00215 Ace^PL00568 Mdoa\Ace^Scer\UAS.cKa Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} Scer\GAL4^C164 Scer\GAL4^Cha.7.4 Scer\GAL4^elav-C155
Constructs (3)
	P{Cha-GAL4.7.4} P{UAS-mCD8::GFP.L} P{UAS-MdAChE.K}
Genes (4)
	Ace Mdoa\Ace Mmus\Cd8a Scer\GAL4
Insertions (4)
	P{GawB}C164 P{GawB}elav^C155 PBac{GAL4D,EYFP}Ace^PL00568 PBac{PB}Ace^c00215
Natural transposons (1)
	P-element