Effects of esketamine on depressive-like behavior and prefrontal cortex sphingolipid levels in chronic variable stress mice
Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 4
Abstract
Objective To investigate the effects of esketamine on depressive-like behavior and prefrontal cortex (PFC) sphingolipid levels in chronic various stress (CVS) mice. Methods Thirty-one C57 mice were randomly divided into control group (n = 10), model + saline group ( n = 10) and model + esketamine treatment group ( n = 11). Mice in model + saline group and model + esketamine treatment group received CVS modeling for 21 d. After modeling, mice in the two groups received intraperitoneal injection of 10 μL / g normal saline and 10 mg / kg esketamine, respectively. The depressive-like behavior of mice was tested by open field test, elevated plus maze test, tail suspension test and forced swim test. Then mice were sacrificed, and the PFC was isolated. The PFC sphingolipid level and composition of small molecules were detected by high-performance liquid chromatography-mass spectrometry. LipidSearch 4. 1 and SIMCA-P 14. 1 were used to analyze the relative lipid content. SPSS 26. 0 was used for data processing, one-way ANOVA was used for differences among multiple groups, and Tukey test was used for differences between two groups. Results ①CVS model could induce stable depression-like behavior in mice, and the results of open field test, elevated plus maze test, tail suspension test and forced swim test were statistically different in the three groups of mice. A single intraperitoneal injection of esketamine reversed depressive-like behavior in mice and altered partial sphingolipid levels and their constituent small molecules. ②There was a statistically significant difference in the overall level of sphingolipids in the three groups (F2,28 = 22. 92, P < 0. 01), and the differences among the three subclasses of sphingolipids: sphingomyelin (F2, 28 = 15. 76, P < 0. 01), cerebrosides (F2,28 = 21. 56,P < 0. 01) and gangliosides (F2, 28 = 4. 056, P < 0. 05) were also statistically significant. Further analysis of the composition of small molecules showed that phytosphingosine ( phSM) and GM3 decreased significantly after CVS modeling, and esketamine treatment increased the levels of the above small lipid molecules (all P < 0. 05). Compared with the control group, the levels of ceramides phosphate ( CerP) and sulfatide decreased in the model + saline group, but esketamine treatment did not affect the levels of the above small lipid molecules. ③There was a certain correlation between PFC sphingolipid levels and behavioral results. The PFC sphingomyelin levels of CVS mice were correlated with residence time in the central area in open field test (Pearson r = 0. 378 1, P < 0. 05), and small molecule phSM was also correlated with residence time in the central area in open field test (P < 0. 05). Small molecules ceramide, CerP and CerG3 levels of PFC cerebrosides in CVS mice were correlated with immobility time of tail suspension in tail suspension test (all P < 0. 05). Conclusion Esketamine treatment can improve depression-like behavior in CVS mice, which may be related to the changes in the relative content and composition of PFC sphingolipids in mice, especially the sphingomyelin level.
Authors and Affiliations
ZHAO Xinxin, ZHOU Cuihong, DONG Hailong, CAI Min
Keywords
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