Propofol Anesthesia Impairs the Maturation and Survival of Adult-born Hippocampal Neurons

Abstract

Background: Adult neurogenesis occurs in the hippocampus of most mammals, including humans, and plays an important role in hippocampal-dependent learning. This process is highly regulated by neuronal activity and might therefore be vulnerable to anesthesia. In this article, the authors investigated this possibility by evaluating the impact of propofol anesthesia on mouse hippocampal neurons generated during adulthood, at two functionally distinct maturational stages of their development. Methods: Adult-born hippocampal neurons were identified using the cell proliferation marker bromodeoxyuridine or a retroviral vector expressing the green fluorescent protein in dividing cells and their progenies. Eleven or 17 days after the labeling procedure, animals (n = 3-5 animals per group) underwent a 6-h-long propofol anesthesia. Twenty-one days after labeling, the authors analyzed the survival, differentiation, and morphologic maturation of adult-born neurons using confocal microscopy.Results: Propofol impaired the survival and maturation of adult-born neurons in an age-dependent manner. Anesthesia induced a significant decrease in the survival of neurons that were 17 days old at the time of anesthesia, but not of neurons that were 11 days old. Similarly, propofol anesthesia significantly reduced the dendritic maturation of neurons generated 17 days before anesthesia, without interfering with the maturation of neurons generated 11 days before anesthesia. Conclusions: These results reveal that propofol impairs the survival and maturation of adult-born hippocampal neurons in a developmental stage-dependent manner in mice.

Chronic Treatment with Anesthetic Propofol Improves Cognitive Function and Attenuates Caspase Activation in Both Aged and Alzheimer's Disease Transgenic Mice

“…First, we did not determine the dose-dependent effects of propofol on caspase-3 activation and cognitive function in the aged and AD Tg mice, because these AD Tg and aged mice are expensive and not easy to obtain. Different doses of propofol may cause neurotoxic [54–56] and neuroprotective [57–59] effects. It is possible that different doses of propofol may neither attenuate the caspase-3 activation nor improve the cognitive function in the aged and AD Tg mice.…”

Angiotensin II-induced mouse hippocampal neuronal HT22 cell apoptosis was inhibited by propofol: Role of neuronal nitric oxide synthase and metallothinonein-3

“…404 In the present study, we identified that Ang II induced (Martin et al, 2006;Miyazaki 445 et al, 2007). Further, it is indicated that its neuroprotec-446 tive effects were mediated via anti-oxidative and anti-447 apoptotic properties (Krzisch et al, 2013). In the present 448 study, we reported that MT-3 was down-regulated by 449 Ang II, suggesting that Ang II caused hippocampal (Chen et al, 2010(Chen et al, , 2011Gokcinar et al, 2013).…”

“…It was reported that propofol impairs the 463 survival and maturation of adult-born hippocampal neu-464 rons in mice(Krzisch et al, 2013). It was also demon-465 strated that propofol induces apoptosis in developing 466 neurons in the in vitro and in vivo settings(Pearn et al, 467 2012).…”

“…Recently, several lines of evi-18 dence have pointed to the contribution of Ang II to multiple 19 pathological processes of the brain (Deliu et al, 2014), 20 such as Alzheimer's disease (AD) (Wang et al, 2011), 21 cerebral ischemia damage (Wu et al, 2013) (Martin et al, 2006;Miyazaki 39 et al, 2007). Its neuroprotective effects were mediated 40 via anti-oxidative, anti-inflammatory, and anti-apoptotic 41 properties (Krzisch et al, 2013). Considering the fact that (FBS), 100 units/ml penicillin, 100 lg/ml streptomycin, 81 and 0.25 lg/ml amphotericin B.…”

P1‐081: Chronic Treatment With Anesthetic Propofol Attenuates B‐amyloid Protein Levels in Brain Tissues of Aged Mice

“…First, we did not determine the dose or time-dependent effects of propofol on Aβ levels in the brain tissues of the aged mice. Different treatments of propofol may be neurotoxic [47][48][49] or neuroprotective [50][51][52]. Therefore, it is possible that propofol treatment with different doses or administered at different times may have different effects on brain Aβ levels.…”