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Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory
Author(s) -
Zhang Yiying,
Xu Zhipeng,
Wang Hui,
Dong Yuanlin,
Shi Hai Ning,
Culley Deborah J.,
Crosby Gregory,
Marcantonio Edward R.,
Tanzi Rudolph E.,
Xie Zhongcong
Publication year - 2012
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23536
Subject(s) - isoflurane , desflurane , mptp , anesthetic , mitochondrial permeability transition pore , mitochondrion , pharmacology , chemistry , neuroscience , anesthesia , apoptosis , medicine , biology , programmed cell death , pathology , parkinson's disease , biochemistry , disease
Objective: There are approximately 8.5 million Alzheimer disease (AD) patients who need anesthesia and surgery care every year. The inhalation anesthetic isoflurane, but not desflurane, has been shown to induce caspase activation and apoptosis, which are part of AD neuropathogenesis, through the mitochondria‐dependent apoptosis pathway. However, the in vivo relevance, underlying mechanisms, and functional consequences of these findings remain largely to be determined. Methods: We therefore set out to assess the effects of isoflurane and desflurane on mitochondrial function, cytotoxicity, learning, and memory using flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry, and the fear conditioning test. Results: Here we show that isoflurane, but not desflurane, induces opening of mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, reduction in levels of mitochondrial membrane potential and adenosine‐5′‐triphosphate, activation of caspase 3, and impairment of learning and memory in cultured cells, mouse hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane‐induced mPTP opening, caspase 3 activation, and impairment of learning and memory. Finally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species. Interpretation: These findings suggest that desflurane could be a safer anesthetic for AD patients as compared to isoflurane, and elucidate the potential mitochondria‐associated underlying mechanisms, and therefore have implications for use of anesthetics in AD patients, pending human study confirmation. ANN NEUROL 2012;