The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Anesthesia Leads to Tau Hyperphosphorylation through Inhibition of Phosphatase Activity by Hypothermia
Open accessAbstract
Postoperative cognitive dysfunction, confusion, and delirium are common after general anesthesia in the elderly, with symptoms persisting for months or years in some patients. Even middle-aged patients are likely to have postoperative cognitive dysfunction for months after surgery, and Alzheimer's disease (AD) patients appear to be particularly at risk of deterioration after anesthesia. Several investigators have thus examined whether general anesthesia is associated with AD, with some studies suggesting that exposure to anesthetics may increase the risk of AD. However, little is known on the biochemical consequences of anesthesia on pathogenic pathways in vivo . Here, we investigated the effect of anesthesia on tau phosphorylation and amyloid precursor protein (APP) metabolism in mouse brain. We found that, regardless of the anesthetic used, anesthesia induced rapid and massive hyperphosphorylation of tau, rapid and prolonged hypothermia, inhibition of Ser/Thr PP2A (protein phosphatase 2A), but no changes in APP metabolism or Aβ (β-amyloid peptide) accumulation. Reestablishing normothermia during anesthesia completely rescued tau phosphorylation to normal levels. Our results indicate that changes in tau phosphorylation were not a result of anesthesia per se, but a consequence of anesthesia-induced hypothermia, which led to inhibition of phosphatase activity and subsequent hyperphosphorylation of tau. These findings call for careful monitoring of core temperature during anesthesia in laboratory animals to avoid artifactual elevation of protein phosphorylation. Furthermore, a thorough examination of the effect of anesthesia-induced hypothermia on the risk and progression of AD is warranted.
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Cites
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Cited by
Tau in physiology and pathology
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Mechanisms of tau-induced neurodegeneration
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Metadata
- Authors
- Planel, E., Richter, K. E. G., Nolan, C. E., Finley, J. E., Liu, L., Wen, Y., Krishnamurthy, P., Herman, M., Wang, L., Schachter, J. B., Nelson, R. B., Lau, L.-F., & Duff, K. E.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-03-21
- Volume
- 27
- Issue
- 12
- Pages
- 3090-3097
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2077859404
- Cited by
- 386
- References
- 71
- FWCI
- 5.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Planel, E., Richter, K. E. G., Nolan, C. E., Finley, J. E., Liu, L., Wen, Y., Krishnamurthy, P., Herman, M., Wang, L., Schachter, J. B., Nelson, R. B., Lau, L.-F., & Duff, K. E. (2007). Anesthesia Leads to Tau Hyperphosphorylation through Inhibition of Phosphatase Activity by Hypothermia. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.4854-06.2007
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