. Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia. J Neurosci. 2007 Mar 21;27(12):3090-7. PubMed.


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  1. Improvements in medical and surgical procedures have resulted in longer human lifespan. However, surgery could promote collateral damage in neurons due to the use of different types of anesthesia. It has been suggested that exposure to anesthetic agents could promote cognitive dysfunction (1). Now, Planel et al. (2) clearly indicate a mechanism to explain how anesthesia is a risk for increasing tau pathology in Alzheimer disease (AD). In well-performed work, Planel et al. show that anesthesia leads to tau hyperphosphorylation similar to that occurring in AD. They have shown that tau hyperphosphorylation was not the consequence of an increase in kinase activity but of a decrease in phosphatase (PP2A) activity, with anesthesia-induced hypothermia being the cause for phosphatase inhibition.

    This work supports a previous observation by Planel et al. (3) indicating that hypothermia, promoted by different causes, results in the appearance of aberrant tau phosphorylation. A clinical implication of Planel’s results is a call for monitoring the body (brain) temperature during anesthesia to avoid prolonged hypothermia and to have a fast return to normal temperature.

    Also, a result of great interest from the work of Planel et al. is that hypothermia did not change APP metabolism or Aβ accumulation, suggesting that PP2A inhibition, induced by anesthesia, did not play a role in Aβ pathology. However, this point has been previously discussed (4). Thus, it has been shown that some anesthetic compounds promote Aβ secretion in APP-overexpressing cells (4). Accordingly, compounds able to inhibit or prevent the expression of PP2A by pharmacological (5) or genetic means (6) should be tested to confirm the previous results on APP metabolism, or to determine other side effects for anesthesia.


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