title: Isoflurane anesthesia exacerbates learning and memory impairment in zinc-deficient APP/PS1 transgenic mice.
abstract: Zinc (Zn) is known to play crucial roles in numerous brain functions including learning and memory. Zn deficiency is believed to be widespread throughout the world, particularly in patients with Alzheimer's disease (AD). A number of studies have shown that volatile anesthetics, such as isoflurane, might be potential risk factors for the development of AD. However, whether isoflurane exposure accelerates the process of AD and cognitive impairment in AD patients with Zn deficiency is yet to be documented. The aim of the present study was to explore the effects of 1.4% isoflurane exposure for 2 h on learning and memory function, and neuropathogenesis in 10-month-old Zn-adequate, Zn-deficient, and Zn-treated APP/PS1 mice with the following parameters: behavioral tests, neuronal apoptosis, Aβ, and tau pathology. The results demonstrated that isoflurane exposure showed no impact on learning and memory function, but induced transient elevation of neuroapoptosis in Zn-adequate APP/PS1 mice. Exposure of isoflurane exhibited significant neuroapoptosis, Aβ generation, tau phosphorylation, and learning and memory impairment in APP/PS1 mice in the presence of Zn deficiency. Appropriate Zn treatment improved learning and memory function, and prevented isoflurane-induced neuroapoptosis in APP/PS1 mice. Isoflurane exposure may cause potential neurotoxicity, which is tolerated to some extent in Zn-adequate APP/PS1 mice. When this tolerance is limited, like in AD with Zn deficiency, isoflurane exposure markedly exacerbated learning and memory impairment, and neuropathology, indicating that AD patients with certain conditions such as Zn deficiency may be vulnerable to volatile anesthetic isoflurane.
authors: Department of Anesthesiology, The First Hospital of Jilin University, No. 71 Xinmin St., Changchun 130021, People's Republic of China.
authors: Chunsheng
authors: C
authors: Feng
authors: School of Public Health, Jilin University, No. 1163 Xinmin St., Changchun 130021, People's Republic of China.
authors: Ya
authors: Y
authors: Liu
authors: Department of Anesthesiology, The First Hospital of Jilin University, No. 71 Xinmin St., Changchun 130021, People's Republic of China.
authors: Ye
authors: Y
authors: Yuan
authors: School of Public Health, Jilin University, No. 1163 Xinmin St., Changchun 130021, People's Republic of China.
authors: Weiwei
authors: W
authors: Cui
authors: School of Public Health, Jilin University, No. 1163 Xinmin St., Changchun 130021, People's Republic of China.
authors: Feng
authors: F
authors: Zheng
authors: School of Public Health, Jilin University, No. 1163 Xinmin St., Changchun 130021, People's Republic of China.
authors: Yuan
authors: Y
authors: Ma
authors: Department of Anesthesiology, The First Hospital of Jilin University, No. 71 Xinmin St., Changchun 130021, People's Republic of China. Electronic address: pumh@jlu.edu.cn.
authors: Meihua
authors: M
authors: Piao
mesh_terms: D000544:Alzheimer Disease / Q000150:complications; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007530:Isoflurane / Q000633:toxicity*; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D018685:Anesthetics, Inhalation; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D007530:Isoflurane; D015032:Zinc
keywords: Alzheimer's disease; General anesthesia; Isoflurane; Learning and memory function; Zinc deficiency