Isoflurane mediated neuropathological and cognitive impairments in the triple transgenic Alzheimer's mouse model are associated with hippocampal synaptic deficits in an age-dependent manner
单位：[1]Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America[2]Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, China[3]Department of Anesthesiology, sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China中山大学附属第二医院
Many in vivo studies suggest that inhalational anesthetics can accelerate or prevent the progression of neuropathology and cognitive impairments in Alzheimer Disease (AD), but the synaptic mechanisms mediating these ambiguous effects are unclear. Here, we show that repeated exposures of neonatal and old triple transgenic AD (3xTg) and non-transgenic (NonTg) mice to isoflurane (Iso) distinctly increased neurodegeneration as measured by S100 beta levels, intracellular A beta, Tau oligomerization, and apoptotic markers. Spatial cognition measured by reference and working memory testing in the Morris Water Maze (MWM) were altered in young NonTg and 3xTg. Field recordings in the cornu ammonis 1 (CA1) hippocampus showed that neonatal control 3xTg mice exhibited hypo-excitable synaptic transmission, reduced paired-pulse facilitation (PPF), and normal long-term potentiation (LTP) compared to NonTg controls. By contrast, the old control 3xTg mice exhibited hyper-excitable synaptic transmission, enhanced PPF, and unstable LTP compared to NonTg controls. Repeated Iso exposures reduced synaptic transmission and PPF in neonatal NonTg and old 3xTg mice. LTP was normalized in old 3xTg mice, but reduced in neonates. By contrast, LTP was reduced in old but not neonatal NonTg mice. Our results indicate that Iso-mediated neuropathologic and cognitive defects in AD mice are associated with synaptic pathologies in an age-dependent manner. Based on these findings, the extent of this association with age and, possibly, treatment paradigms warrant further study.
基金：
NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K08-GM073224, R01GM084979, 3R01GM084979-02S1, 2R01GM084979-06A1]; March of Dimes Birth Defects Foundation Research Grant, White Plains, New YorkMarch of Dimes [12-FY08-167]; Department of Anaesthesiology, Perelman School of Medicine, University of Pennsylvania; National Institute of General Medical Science, National Institute of Health, Baltimore, Maryland; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM084979] Funding Source: NIH RePORTER
第一作者单位：[1]Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America
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推荐引用方式(GB/T 7714)：
Joseph Donald J.,Liu Chunxia,Peng Jun,et al.Isoflurane mediated neuropathological and cognitive impairments in the triple transgenic Alzheimer's mouse model are associated with hippocampal synaptic deficits in an age-dependent manner[J].PLOS ONE.2019,14(10):doi:10.1371/journal.pone.0223509.
APA：
Joseph, Donald J.,Liu, Chunxia,Peng, Jun,Liang, Ge&Wei, Huafeng.(2019).Isoflurane mediated neuropathological and cognitive impairments in the triple transgenic Alzheimer's mouse model are associated with hippocampal synaptic deficits in an age-dependent manner.PLOS ONE,14,(10)
MLA：
Joseph, Donald J.,et al."Isoflurane mediated neuropathological and cognitive impairments in the triple transgenic Alzheimer's mouse model are associated with hippocampal synaptic deficits in an age-dependent manner".PLOS ONE 14..10(2019)
