Isoflurane anesthesia precipitates tauopathy and upper airways dysfunction in pre-symptomatic Tau-P301L mice- Possible implication for neurodegenerative diseases-

Authors
C. Menuet, P. Borghgraef, N. Voituron, C. Gestreau, L. Gielis et al.


Lab
Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, MP3-respiration team, Faculté Saint Jérôme, Marseille, France.

Journal
Neurobiology of Disease

Abstract
The postoperative cognitive decline resulting from volatile anesthesia is gaining acceptance as a major health problem. The common anesthetic isoflurane is suspected to precipitate neurodegeneration in Alzheimer's disease by unknown mechanisms. We previously validated that 8month old Tau.P301L mice suffer upper airways defects related to tauopathy within the Kolliker-Fuse nucleus that controls upper airways function. We now report that isoflurane anesthesia in young, pre-symptomatic Tau.P301L mice triggered precocious upper airways defects and tauopathy in several brainstem nuclei, including the nucleus ambiguus that contains upper airways motor neurons and the Kolliker-Fuse. The prescription drug memantine, identified as an NMDA receptor antagonist, prevented the post-anesthesia upper airways dysfunction and alleviated tauopathy in the nucleus ambiguus and Kolliker-Fuse. We further identified protocols of anesthesia in young Tau.P301L mice that mitigated adverse effects of isoflurane anesthesia. Thus, our experimental findings in a validated mouse model for tauopathy demonstrate the link between isoflurane anesthesia, earlier onset of tauopathy and earlier onset of functional deficits, highlight the implication of NMDA-receptors in the mechanisms mediating the adverse effects of isoflurane, and potentially identify safer protocols for anesthesia in patients with tauopathy.

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.