title: miRNA expression profile and involvement of Let-7d-APP in aged rats with isoflurane-induced learning and memory impairment.
abstract: MicroRNAs (miRNAs) play a key role in different nervous system diseases. We sought to determine the role of miRNAs in isoflurane-induced learning and memory impairment in aged rats. Male Sprague-Dawley (SD) rats of 18 month were randomly assigned to control group (exposed to mock anesthesia), 2-hour group and 6-hour group (exposed to 2% isoflurane for 2 and 6 hours respectively). By Morris Water Maze, 6-hour group showed impaired learning and memory ability while 2-hour group not. As shown by miRNA array, control group and 2-hour group showed a similar miRNA expression profile. And 38 miRNAs are differently expressed in 6-hour group compared to the other 2 groups, including 21 up-regulated miRNAs and 17 down-regulated miRNAs. And 4 of the differentially expressed miRNAs were validated independently by qRT-PCR. Let-7d was downregulated in 6-hour group. Additionally, we demonstrated that amyloid precursor protein (APP) was a direct target of let-7d by Fluorescent report assay. Increased expression of APP and amyloid-β (Aβ) were found in the hippocampi of 6-hour group. Downregulation of let-7d might contribute to isoflurane-induced learning and memory impairment through upregulating its target APP, and increasing the production of Aβ subsequently.
authors: Department of Anesthesiology, Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Ting
authors: T
authors: Luo
authors: Suzhou Kowloon Hospital, Shanghai JiaoTong University School of Medicine, Suzhou, Jiangsu, China.
authors: Shuzhou
authors: S
authors: Yin
authors: Department of Anesthesiology, Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Rong
authors: R
authors: Shi
authors: Department of Anesthesiology, Beijing Jishuitan Hospital, Fourth Medical College of Peking University, Beijing, China.
authors: Chengshi
authors: C
authors: Xu
authors: Department of Anesthesiology, Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Yun
authors: Y
authors: Wang
authors: Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Jun
authors: J
authors: Cai
authors: Department of Anesthesiology, Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Yun
authors: Y
authors: Yue
authors: Department of Anesthesiology, Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Anshi
authors: A
authors: Wu
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007530:Isoflurane / Q000009:adverse effects*; D007859:Learning Disabilities / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016564:Amyloid beta-Protein Precursor; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D007530:Isoflurane