Tau hyperphosphorylation is associated with memory impairment after exposure to 1.5% isoflurane without temperature maintenance in rats

Abstract

Our results indicate that tau phosphorylation is not a direct result of anaesthesia per se, but it is due to anaesthesia-induced hypothermia and this leads to the inhibition of phosphatase activity as well as tau hyperphosphorylation. Tau hyperphosphorylation is associated with the observed deficits in spatial learning and memory following anaesthesia in hypothermic rats.

Tau Phosphorylation and Sevoflurane Anesthesia

“…43 Interestingly, previous observations support that hyperphosphorylated forms of tau contribute to cognitive deficits following isoflurane-based anesthesia in 6-month-old rats, without body temperature maintenance, using the Y-maze test paradigm. 21 In addition, tau hyperphosphorylation was shown to promote memory decline in aged mice using the Morris water maze task even in absence of neurofibrillary degeneration. 36 Tau proteins can be phosphorylated by several kinases (for reviews, 24,25,28,29 ).…”

“…However, former studies evaluating relationship between anesthesia and tau were performed using acute paradigms and not always in normothermic conditions. 19,21 The aim of the present study was to determine not only whether acute anesthesia with sevoflurane causes hippocampal tau hyperphosphorylation in normothermic conditions but also whether repeated exposures lead to persistent hippocampal tau hyperphosphorylation and spatial memory deficit in adult mice.…”

Una complicación quirúrgica escasamente sospechada: la disfunción cognitiva postoperatoria

“…Adicionalmente, algunos estudios han demostrado que los agentes anestésicos volátiles inducen la hiperfosforilación de tau, lo que probablemente se deba a la activación de proteínas quinasas activadas por estrés (35); así como se ha reportado un impacto más severo en la función cognitiva de pacientes sometidos a cirugía radical de recto cuando se empleó en la anestesia sevoflurano comparado con el propofol en PAM con DCL (36).…”

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

“…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].…”