Novel benzodiazepine remimazolam tosylate delays neurodegeneration of aged mice via decreasing tau phosphorylation

Abstract

Benzodiazepines like midazolam were generally considered one of the possible causes affecting postoperative cognitive recovery. As a new kind of rapid-effect benzodiazepine, remimazolam tosylate was widely used in clinical anesthesia for its pharmacological advantage, but few studies reported its effects on cognitive function in the elderly. Here, we aimed to research the effects of remimazolam tosylate on cognitive function in aged mice and its underlying biological mechanisms. We measured the memory function of aged mice immediately and one month after intraperitoneal injection of remimazolam tosylate compared to the saline control. The brain metabolism level was detected by Positron Emission Tomography/Computed tomography (PET/CT). Compared with the control, we observed a decrease in memory ability， as well as an increase in tau phosphorylation level and a decrease in phosphatase level in the short term; however, one month later, contrary to the previous results, we observed better memory and brain metabolism and lower tau phosphorylation levels in the experimental group compared to the control. Therefore, we concluded that remimazolam tosylate did not cause long-term damage to the cognitive function of aged mice and even delayed the decline of memory function in the aging process to some extent.