Administration of the benzodiazepine midazolam increases tau phosphorylation in the mouse brain.

Administration of the benzodiazepine midazolam increases tau phosphorylation in the mouse brain. Neurobiol Aging. 2018 Nov 08;75:11-24 Authors: Whittington RA, Virág L, Gratuze M, Lewkowitz-Shpuntoff H, Cheheltanan M, Petry F, Poitras I, Morin F, Planel E Abstract Preclinical studies have shown that anesthesia might accelerate the clinical progression of Alzheimer's disease (AD) and can have an impact on tau pathology, a hallmark of AD. Although benzodiazepines have been suggested to increase the risk of incident dementia, their impact on tau pathology in vivo is unknown. We thus examined the impact of midazolam, a benzodiazepine that is often administered perioperatively as an anxiolytic, on tau hyperphosphorylation in nontransgenic and in hTau mice, the latter a model of AD-like tau pathology. The acute administration of midazolam in C57BL/6 mice was associated with downregulation of protein phosphatase-1 and a significant and persistent increase in brain tau phosphorylation. In hTau mice, tau hyperphosphorylation was also observed; however, midazolam was neither associated with proaggregant changes nor spatial reference memory impairment. In C57BL/6 mice, chronic midazolam administration immediately increased hippocampal tau phosphorylation, and this effect was more pronounced in older mice. Interestingly, in young C57BL/6 mice, chronic midazolam administration induced hippocampal tau hyperphosphorylation, which persisted for 1Â...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research