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Published on: June 4, 2020
Sevoflurane Impairs Short-Term Memory by Affecting PSD-95 and AMPA Receptor in the Hippocampus of a Mouse Model
Yuan Jiao1, Hongwu Fan2, Kexin Wang1
1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Objective:
To explore the effects of sevoflurane on the latency and error times of the passive avoidance and levels of PSD-95 and AMPA receptors in the hippocampus. We evaluated the effects of sevoflurane on short-term memory in adult mice and explored the possible mechanism.
Methods:
144 Kunming mice (2-3 months, 30-35 g) were randomly divided into two groups A (n = 64) and B (n = 80) and received the dark-avoidance (DA) and step-down avoidance (SA) tests, respectively. The groups DA and SA were further divided into control (inhaled 40% O2 2 h) and sevoflurane (3.3% sevoflurane and 40% O2 2 h) subgroups. Before inhalation intervention, all mice were trained to be familiar with the Morris water maze (MWM). According to the test points of behavioral indicators, 8 mice were randomly selected from each subgroup at point 12 h (T1), 24 h (T2), 48 h (T3), and 72 h (T4) after inhalation intervention. The step-through latency and error times were measured in 5 min. After the behavioral test, the mice were killed and the tissues of the hippocampus were taken for hematoxylin and eosin (H&E) staining. The expression level of PSD-95 and AMPA receptors in the hippocampus was detected by immunohistochemistry and Western Blot. The changes of synaptic transmission were measured via electrophysiology analysis of hippocampal slices.
Results:
The mice in the control subgroups found the platform in a shorter pathway than those in the sevoflurane subgroups during an MWM test. The step-through latency of T1 and T2 in the sevoflurane subgroup was shorter than baseline time, and the error times were increased in 5 min and higher than baseline time when compared with the control subgroup (P < 0.05) in the A and B groups. Compared with the control subgroup, the expression level of PSD-95 and AMPA receptors in the hippocampus was decreased at T1 and T2 in the sevoflurane subgroup (P < 0.05). The nerve cells were partially swelling. Electrophysiology analysis showed that the levels of PSD-95 and AMPA receptor expression were associated with synaptic transmission.
Conclusion:
Sevoflurane impaired short-term memory in adult mice by inhibiting the expression of PSD-95 and AMPA receptors in the hippocampus, which led to the decrease in synaptic transmission.
Insights
Sevoflurane anesthesia impairs short-term memory in adult mice by reducing hippocampal PSD-95 and AMPA receptor expression, leading to decreased synaptic transmission.
Area of Science:
- Anesthesiology
- Neuroscience
- Molecular Biology
Background:
- Sevoflurane is a widely used inhalation anesthetic.
- Understanding its effects on cognitive function and underlying molecular mechanisms is crucial.
Purpose of the Study:
- To investigate the impact of sevoflurane on short-term memory in adult mice.
- To explore the role of hippocampal PSD-95 and AMPA receptors in sevoflurane-induced memory impairment.
Main Methods:
- Adult mice underwent passive avoidance tests (dark-avoidance and step-down avoidance) after sevoflurane exposure.
- Hippocampal expression of PSD-95 and AMPA receptors was assessed using immunohistochemistry and Western Blot.
- Synaptic transmission was evaluated via electrophysiology analysis.
Main Results:
- Sevoflurane exposure significantly increased error times and decreased step-through latency in memory tests.
- A notable reduction in hippocampal PSD-95 and AMPA receptor expression was observed post-sevoflurane.
- Electrophysiology confirmed a correlation between receptor levels and impaired synaptic transmission.
Conclusions:
- Sevoflurane impairs short-term memory in adult mice.
- This impairment is associated with the inhibition of hippocampal PSD-95 and AMPA receptor expression.
- Reduced synaptic transmission underlies sevoflurane-induced cognitive deficits.

