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PMID: 17376970 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural

Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 12 ·2007-03-21 ·Pages 3090-7

Planel E, Richter KE, Nolan CE, Finley JE, Liu L, Wen Y, Krishnamurthy P, Herman M, Wang L, Schachter JB, Nelson RB, Lau LF, Duff KE

Abstract

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 Abeta (beta-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.

MeSH Terms
Anesthesia/adverse effects Anesthetics/administration & dosage,adverse effects Animals Hippocampus/drug effects,enzymology,metabolism Hypothermia/enzymology,metabolism Male Mice Phosphoprotein Phosphatases/antagonists & inhibitors,metabolism Phosphorylation/drug effects Protein Phosphatase 2 tau Proteins/metabolism
Chemicals
Anesthetics tau Proteins Phosphoprotein Phosphatases Protein Phosphatase 2
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Planel Emmanuel
Columbia University Medical Center, Department of Pathology, Taub Institute for Alzheimer's Disease Research, New York, New York 10032, USA. emmanuel@planel.org
Richter Karl E G
Nolan Charles E
Finley James E
Liu Li
Wen Yi
Krishnamurthy Pavan
Herman Mathieu
Wang Lili
Schachter Joel B
Nelson Robert B
Lau Lit-Fui
Duff Karen E
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4854-06.2007
Email
emmanuel@planel.org
Published
2007-03-21
Pages
3090-7
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6672474
Subset
IM
Grants
NINDS NIH HHS · P01 NS048447 · United States
NIA NIH HHS · P30 AG008051 · United States
NIA NIH HHS · AG008051 · United States
NINDS NIH HHS · NS048447 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4854-06.2007 PMC Full Text View journal details
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