Beneficial effects of quetiapine in a transgenic mouse model of Alzheimer's disease.
Previous studies have suggested that quetiapine, an atypical antipsychotic drug, may have beneficial effects on cognitive impairment, and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the effects of quetiapine on memory impairment and pathological changes in an amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mouse model of Alzheimer's disease (AD). Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5mg/(kg day)) for 1, 4, and 7 months in drinking water from the age of 2 months. After 4 and 7 months of continuous quetiapine administration, memory impairment was prevented, and the number of beta-amyloid (Abeta) plaques decreased in the cortex and hippocampus of the transgenic mice. Quetiapine also decreased brain Abeta peptides, beta-secretase activity and expression, and the level of C99 (an APP C-terminal fragment following cleavage by beta-secretase) in the transgenic mice. Furthermore, quetiapine attenuated anxiety-like behavior, up-regulated cerebral Bcl-2 protein, and decreased cerebral nitrotyrosine in the transgenic mice. These findings suggest that quetiapine can alleviate cognitive impairment and pathological changes in an APP/PS1 double transgenic mouse model of AD, and further indicate that quetiapine may have preventive effects in the treatment of AD.
He
Jue
J
Laboratory of Neuropharmacology, Wenzhou Medical College, Wenzhou, PR China.
Luo
Huanmin
H
Yan
Bin
B
Yu
Yingxin
Y
Wang
Haitao
H
Wei
Zelan
Z
Zhang
Yanbo
Y
Xu
Haiyun
H
Tempier
Adrien
A
Li
Xiaokun
X
Li
Xin-Min
XM
D000375:Aging; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003987:Dibenzothiazepines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000187:drug effects; D053764:Presenilin-1 / Q000235:genetics; D058255:Protease Nexins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000069348:Quetiapine Fumarate; D011956:Receptors, Cell Surface / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D053764:Presenilin-1; D058255:Protease Nexins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D000069348:Quetiapine Fumarate; C002744:3-nitrotyrosine; D014443:Tyrosine; D053829:Amyloid Precursor Protein Secretases