Sevoflurane may exert neurotoxic effects on the developing brain.
Coenzyme Q10 (
CoQ10) has been reported to reduce
sevoflurane anesthesia‑induced cognitive deficiency in 6‑day‑old mice. However, its specific mechanisms remain unknown.
Apolipoprotein E (
ApoE) has been reported to lead to the initiation of neurodegeneration in patients with
Alzheimer's disease (AD) and may serve an important role in anesthesia‑induced neurotoxicity. The present study aimed to reveal the role of
ApoE in the pathogenesis of
tau protein hyperphosphorylation and
neuroinflammation enhancement caused by
sevoflurane anesthesia, as well as the protective mechanism of
CoQ10 in an
anesthetic sevoflurane treatment model of primary mouse hippocampal neurons. For that purpose, the neurons were randomly assigned to the following groups: i) Control; ii) sevoflurane; iii) control+corn oil; iv) sevoflurane+corn oil; v) control+CoQ10; and vi) control+CoQ10.
CoQ10 or
corn oil alone was added to the medium on day 4 of neuron culture. The neurons in the
sevoflurane group were treated with 21% O2, 5% CO2 and 4.1%
sevoflurane for 4 h, whereas the control group only with 21% O2 and 5% CO2 on day 5. Samples were collected immediately after
anesthesia or control treatment.
ATP, superoxidase dismutase (SOD)1,
ApoE mRNA, total
ApoE, full‑length
ApoE,
ApoE fragments, Tau5, Tau‑PS202/PT205 (AT8), Tau‑PSer396/404 (PHF1),
tumor necrosis factor (TNF)‑α,
interleukin (IL)‑6 and IL‑1β levels were measured with ELISA, quantitative PCR, western blotting and immunocytochemistry. The results of the present study indicated that
sevoflurane anesthesia significantly decreased the
ATP and SOD levels, but increased
ApoE mRNA, total
ApoE protein, full‑length
ApoE,
ApoE fragments, phosphorylated tau (AT8 and PHF1) and neuroinflammatory factor (TNF‑α, IL‑6 and IL‑1β) expression levels compared with those in the control group. The use of
CoQ10 reversed the expression of these factors. These results suggested that
sevoflurane treatment damaged mouse hippocampal neurons, which may be associated with the expression of
ApoE and its toxic fragments.
CoQ10 improved energy replenishment and inhibited oxidative stress, which may lead to a decrease in
ApoE and phosphorylated
tau protein expression, thus mitigating the sevoflurane‑induced
neuroinflammation in mouse hippocampal neurons.