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

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• 作者：Clé ; ment Menuet^a ; Peter Borghgraef^b ; Nicolas Voituron^a ; Christian Gestreau^a ; Lies Gielis^b ; Herman Devijver^b ; Mathias Dutschmann^c ; Fred Van Leuven^b ; Gé ; rard Hilaire^a ; ^{gerard.hilaire@univ-cezanne.fr}
• 关键词：AD ; Alzheimer's disease ; Asp ; Airflow Spirogram ; AT8  ; + ; AT8 positively stained ; CSp ; Chest Spirogram ; KF ; Kolliker&ndash ; Fuse ; nA ; Nucleus Ambiguus ; NRA ; Nucleus Retroambiguus ; PAG ; Periaqueductal Gray ; Rf ; Respiratory frequency ; WT ; Wildtype
• 刊名：Neurobiology of Disease
• 出版年：2012
• 出版时间：April, 2012
• 年：2012
• 卷：46
• 期：1
• 页码：234-243
• 全文大小：1314 K

文摘

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 8 month 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.