Anesthesia and tau pathology

Whittington, Robert A.; Bretteville, Alexis; Dickler, Maya; Planel, Emmanuel

doi:10.1016/j.pnpbp.2013.03.004

Cited by 94 publications

(69 citation statements)

References 94 publications

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“…Tau phosphorylation may contribute to the cognitive impairment observed in rodents following anesthesia and surgery [reviewed in 33 ]. Anesthesia with 3% sevoflurane two hours daily for three days (multiple exposures of sevoflurane) in P6 WT mice has been reported to induce cognitive impairment in the mice 9 .…”

Section: Resultsmentioning

confidence: 99%

“…Tau phosphorylation is regulated by several protein kinases such as glycogen synthase kinase 3β (GSK3β) 24–27 , cyclin-dependent kinase 5 (CDK5) 25,28 , cJun n-terminal kinase (JNK), 29,30 and extracellular signal-regulated kinase (ERK) 31 [reviewed in 32,33 ]. The expression of the kinases peaked postnatally at days 8–11 and then returned to low level after 5 weeks 34 .…”

Section: Introductionmentioning

confidence: 99%

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Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

et al. 2014

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Background Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane is a commonly used anesthetic in children. Tau phosphorylation contributes to cognitive dysfunction. We therefore assessed the effects of sevoflurane on Tau phosphorylation and underlying mechanisms in young mice. Methods Six day-old wild-type (WT) and Tau knockout (KO) mice were exposed to sevoflurane. We determined the effects of the sevoflurane anesthesia on Tau phosphorylation, levels of the kinases and phosphatase related to Tau phosphorylation, interleukin-6, and postsynaptic density protein 95 (PSD-95) in hippocampus, and cognitive function in both young WT and Tau KO mice. Results Anesthesia with 3% sevoflurane two hours daily for three days induced Tau phosphorylation (257% versus 100%, P=0.0025, n=6), enhanced activation of glycogen synthase kinase 3β (GSK3β), the kinase related to Tau phosphorylation in the hippocampus of postnatal day 8 WT mice. The sevoflurane anesthesia decreased hippocampus PSD-95 levels and induced cognitive impairment in the postnatal day 31 mice. GSK3β inhibitor lithium inhibited the sevoflurane-induced GSK3β activation, Tau phosphorylation, elevated levels of interleukin-6 and cognitive impairment in the WT young mice. Finally, the sevoflurane anesthesia did not induce an elevation of interleukin-6 levels, reduction in PSD-5 levels in hippocampus, or cognitive impairment in Tau KO young mice. Conclusions These data suggested that sevoflurane induced Tau phosphorylation, GSK3β activation, elevation of interleukin-6 and reduction of PSD-95 levels in hippocampus of young mice, and cognitive impairment in the mice. Future studies will dissect the cascade relationship of these effects.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

et al. 2014

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“…A principle side effect of vGA exposure during surgical procedures is signifi cant drop in body temperature, hypothermia. The enzymatic activity of PPA2A is directly tied to temperature, thus the lowered thermostat has been found to inhibit the dephosphorylation of tau by indirect means, abnormally increasing hyperphosphorylated tau [27,32,33]. SEVO induces increased p-tau/t-tau ratios via inhibition of mammalian target of rapamycin (mTOR); a pathway mediated by GSK-3, indicating vGAs can directly infl uence intracellular kinase activities [34,35].…”

Section: How Volatile General Anesthetics (Vga) Can Induce Ad Pathologymentioning

confidence: 99%

Can Exposure to Volatile Anesthetics Be a Tipping Point for AD Susceptible Populations?

Niesman¹

2017

Ann Alzheimers Dement Care

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The relationship between surgery induced Postoperative Cognitive Dysfunction (POCD) and the development of Alzheimer's disease (AD) later has been a debatable question. Volatile anesthetics represent a potential environmental factor that can change the CNS both acutely and long-term. By interacting with membrane cholesterol to alter signaling in neurons or alter the normally quiescent microglial phenotype, volatile anesthetics are implicated in the development of POCD. The tipping point for triggering AD cyclic pathology may rest with individual AD genetic risk factors combined with the known molecular consequences of anesthetic exposure. This review covers genome wide association studies (GWAS) identifi ed AD risk factors, actions of volatile anesthetics in the development of AD phenotypes and presents some newly discovered pre or post-anesthetic POCD attenuating therapies.

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“…16 NFT maturation involves the acetylation of the lysine residue 280. 15 Once NFTs fully mature, they affect large projecting neurons in a progressive hierarchical pattern.…”

Section: Nftsmentioning

confidence: 99%

“…Propagation can occur by direct seeding of tau oligomers into the lipid rafts of cell membranes, thus increasing cell permeability and allowing access for the spread of larger secreted NFTs. 16 After NFTs propagate, the post-translational modifications become finalized, and behavioral and motor symptoms begin to surface in patients.…”

Section: Nftsmentioning

confidence: 99%

Linking Traumatic Brain Injury to Chronic Traumatic Encephalopathy: Identification of Potential Mechanisms Leading to Neurofibrillary Tangle Development

Lucke‐Wold

Turner²,

Logsdon³

et al. 2014

Journal of Neurotrauma

105

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Significant attention has recently been drawn to the potential link between head trauma and the development of neurodegenerative disease, namely chronic traumatic encephalopathy (CTE). The acute neurotrauma associated with sportsrelated concussions in athletes and blast-induced traumatic brain injury in soldiers elevates the risk for future development of chronic neurodegenerative diseases such as CTE. CTE is a progressive disease distinguished by characteristic tau neurofibrillary tangles (NFTs) and, occasionally, transactive response DNA binding protein 43 (TDP43) oligomers, both of which have a predilection for perivascular and subcortical areas near reactive astrocytes and microglia. The disease is currently only diagnosed postmortem by neuropathological identification of NFTs. A recent workshop sponsored by National Institute of Neurological Disorders and Stroke emphasized the need for premortem diagnosis, to better understand disease pathophysiology and to develop targeted treatments. In order to accomplish this objective, it is necessary to discover the mechanistic link between acute neurotrauma and the development of chronic neurodegenerative and neuropsychiatric disorders such as CTE. In this review, we briefly summarize what is currently known about CTE development and pathophysiology, and subsequently discuss injury-induced pathways that warrant further investigation. Understanding the mechanistic link between acute brain injury and chronic neurodegeneration will facilitate the development of appropriate diagnostic and therapeutic options for CTE and other related disorders.

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Anesthesia and tau pathology

Cited by 94 publications

References 94 publications

Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

Can Exposure to Volatile Anesthetics Be a Tipping Point for AD Susceptible Populations?

Linking Traumatic Brain Injury to Chronic Traumatic Encephalopathy: Identification of Potential Mechanisms Leading to Neurofibrillary Tangle Development

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