Abstract
Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.
Highlights
Delirium is an acute, transient, usually reversible, fluctuating disturbance in attention, cognition, and consciousness level [1]
We aimed to evaluate the effects of surgery under 1.4% isoflurane anesthesia (Surgery/Anesthesia) for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice by evaluating the mitochondrial morphometrics in the hippocampus and prefrontal cortex, expression of the mitochondrial fission/fusion dynamics-related proteins, and identifying the subsequent changes in mitochondrial function-related indicators, namely, oxidative stress and anti-oxidative stress-related markers (ROS and superoxide dismutase [Superoxide dismutase (SOD)]), energy metabolism-related indicators (ATP and mitochondrial membrane potential [ Mitochondrial membrane potential (MMP)]), and neuronal/synaptic plasticity-related proteins
We demonstrated that Surgery/Anesthesia could disturb mitochondrial fission/fusion dynamics in the brain of aged mice with Postoperative delirium (POD)
Summary
Transient, usually reversible, fluctuating disturbance in attention, cognition, and consciousness level [1]. Postoperative delirium (POD) is a common complication following surgery and anesthesia, especially in the elderly population [2,3,4]. Advanced age was reported to be an independent risk factor for the development of POD [9], as the elderly may have a lack of physiologic reserves [10, 11]. With a significant increase in the aging population, complications related to the elderly are becoming increasingly important [12]. Mitochondrial dynamics include mitochondrial biogenesis, selective degradation (including mitophagy), mitochondrial fusion and fission events, as well as processes such as intracellular transport [15, 16]. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function [15]
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