Abstract
Since accumulating evidence suggests the application of anesthetics may increase the risk of Alzheimer’s disease (AD), we investigated the cytotoxicity of inhaled general anesthesia in neurons and its underlying mechanism. Using primary cultured rat hippocampal neurons as the study model, here we show that isoflurane increases vulnerability to intracellular or extracellular amyloid β with or without serum deprivation. This isoflurane-induced effect is mediated by the downregulation of miR-214 level that lead to an elevated expression of Bax, a prominent target for miR-214. We conclude that isoflurane increases cell death in the presence of amyloid β by increasing Bax level through downregulating miR-214. Our data provide a new insight for inhaled anesthetics toxicity and indicate a possible mechanistic link between anesthetic application and neurodegenration in AD.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by senile plaques and neurofibrillary tangles in elderly [1]
The neurons were insulted with intracellular Ab1-42, extracellular Ab1-42, or in combination with serum deprivation (-S)
When neurons were treated with Ab1-42 peptide in culture medium, isoflurane did not enhance cell death compared with eAb1-42 alone (Fig. 1B)
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by senile plaques and neurofibrillary tangles in elderly [1]. With increasing number of older people worldwide undergo surgery every year, accumulating evidence indicates the association between anesthetic application and risk for AD. While the age of AD onset has been linked to surgery history in which inhaled anesthetics was used [14,15,16,17], there is evidence indicates that there is no correlation between the usage of general anesthesia and AD [18]. Despite the conflicting clinical evidence on the risk of AD after the usage of inhaled anesthetics, potential mechanisms responsible for neuronal damage following inhaled anesthetia have been suggested. Some anesthetics promote protein misfolding and aggregation, one of the mechanisms associating with cell death in neurodegenerative diseases [12,19,20]. Our understanding of how anesthetics increase neuronal cell death remains very limited
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