Effects of propofol and surgery on neuropathology and cognition in the 3xTgAD Alzheimer transgenic mouse model

Abstract

Surgery in a vulnerable transgenic mouse under propofol anaesthesia was associated with minimal to no changes in short- and long-term behaviour and no changes in neuropathology. This suggests that propofol anaesthesia is associated with better cognitive outcomes in the aged, vulnerable brain compared with inhalation anaesthesia.

Thinking, fast and slow: highlights from the 2016 BJA seminar on anaesthetic neurotoxicity and neuroplasticity

“…29 Exposure to anaesthesia and surgery worsens cognitive impairment in transgenic Alzheimer mice. 10 Ongoing work suggests that anaesthetics impair dendrite development, which has been implicated in neurodevelopmental disorders. However, the impact of these structural changes on subsequent neurocognitive deficits has been questioned and needs to be examined in other laboratory models.…”

Repeat propofol anesthesia does not exacerbate plaque deposition or synapse loss in APP/PS1 Alzheimer’s disease mice

“…Notably, as APP/PS1 mice do not exhibit substantial tau pathology, it is possible that propofol may still influence the onset and/or progression of AD tau pathology. However, a recent study investigated the impact of ~ 30 min of propofol exposure in 3xTgAD mice, which develop both Aβ and tau pathology indicates that this is not the case [ 38 ]. Mardini and colleagues detected no difference in performance between propofol exposed and control 3xTgAD mice in the Morris Water Maze both 3 weeks and 16 weeks following propofol exposure [ 38 ].…”

“…However, a recent study investigated the impact of ~ 30 min of propofol exposure in 3xTgAD mice, which develop both Aβ and tau pathology indicates that this is not the case [ 38 ]. Mardini and colleagues detected no difference in performance between propofol exposed and control 3xTgAD mice in the Morris Water Maze both 3 weeks and 16 weeks following propofol exposure [ 38 ]. Likewise, at 18 weeks following propofol exposure there was no change in Aβ plaque load, phosphorylated-tau aggregation or the number of activated microglia between the propofol exposed and control 3xTgAD mice [ 38 ].…”

“…Propofol anesthesia has been reported to result in an increase [ 31 – 33 ], decrease [ 34 , 35 ] and no change [ 36 ] in the incidence of POCD and dementia in humans. Likewise rodent studies have reported that exposure to propofol resulted in no change/decreased levels of Aβ [ 11 , 37 ], and no change in plaque or tau pathology [ 38 ]. While behavioral studies following propofol anesthesia in rodents have observed no change [ 11 , 38 ], decreased [ 39 ] or improved [ 13 ] cognitive function.…”

“…Likewise rodent studies have reported that exposure to propofol resulted in no change/decreased levels of Aβ [ 11 , 37 ], and no change in plaque or tau pathology [ 38 ]. While behavioral studies following propofol anesthesia in rodents have observed no change [ 11 , 38 ], decreased [ 39 ] or improved [ 13 ] cognitive function. However, when elderly patients were studied propofol use associated with POCD in approximately 50% of cases, even following minor surgery [ 40 , 41 ].…”