Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil.
Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly s...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3219671?pdf=render |
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| author | Diansan Su Yanxing Zhao Beilei Wang Huan Xu Wen Li Jie Chen Xiangrui Wang |
| author_facet | Diansan Su Yanxing Zhao Beilei Wang Huan Xu Wen Li Jie Chen Xiangrui Wang |
| author_sort | Diansan Su |
| collection | DOAJ |
| description | Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane. |
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| id | doaj.art-5e16da2b43e84e99b257301537867da3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T00:54:35Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-5e16da2b43e84e99b257301537867da32022-12-22T01:26:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2763210.1371/journal.pone.0027632Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil.Diansan SuYanxing ZhaoBeilei WangHuan XuWen LiJie ChenXiangrui WangAlthough many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane.http://europepmc.org/articles/PMC3219671?pdf=render |
| spellingShingle | Diansan Su Yanxing Zhao Beilei Wang Huan Xu Wen Li Jie Chen Xiangrui Wang Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil. PLoS ONE |
| title | Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil. |
| title_full | Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil. |
| title_fullStr | Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil. |
| title_full_unstemmed | Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil. |
| title_short | Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil. |
| title_sort | isoflurane induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil |
| url | http://europepmc.org/articles/PMC3219671?pdf=render |
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