Antisense inhibition of acetylcholinesterase gene expression for treating cognition deficit in Alzheimer's disease model mice.
To examine whether the selected antisense oligodeoxynucleotides (AS-ODN) targeting against human brain acetylcholinesterase (AChE) mRNA could improve the cognitive deficit in the Alzheimer's disease (AD) model mice induced by amyloid-beta peptide (Abeta), we determined the time-effect relationship of AChE activity and the learning and memory after AS-ODN delivery. The results showed that the AChE activity decreased gradually along with time, initiating at 8 h and lasting 42 h. The time-effect curves of acetylcholine (ACh) behaved consistency with that of AChE activity. The animal cognition studies showed that in step-through test, the error number of the AS-ODN-treated AD model mice was significantly decreased, and the memory retention was increased. In the water maze performance, the swimming time obviously shortened. Our results indicated that antisense therapy is of potential use in the treatment of cognitive deficit in the Abeta model mice.
Fu
Ai-Ling
AL
Institute of Pharmacology and Toxicology, Academy of Military Medicine, Beijing 100850, China.
Zhang
Xing-Mei
XM
Sun
Man-Ji
MJ
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000235:genetics; D000544:Alzheimer Disease / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D016229:Amyloid beta-Peptides; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003072:Cognition Disorders / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D003216:Conditioning, Operant / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015316:Genetic Therapy; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D020319:Oligodeoxyribonucleotides, Antisense; D000110:Acetylcholinesterase; D000109:Acetylcholine