Sevoflurane Impairs Short-Term Memory by Affecting PSD-95 and AMPA Receptor in the Hippocampus of a Mouse Model

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% O(2) 2 h) and sevoflurane (3.3% sevoflurane and 40% O(2) 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.