Journal
JOURNAL OF AFFECTIVE DISORDERS
Volume 259, Issue -, Pages 458-467Publisher
ELSEVIER
DOI: 10.1016/j.jad.2019.08.002
Keywords
Prenatal stress; Depression; Hippocampus; Metabolomics
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Funding
- National Natural Science Foundation of China [81701331, 31600822]
- College Project of The Affiliated Children Hospital of Xi'an Jiaotong University [2015C02]
- The Project of Xi'an Health Bureau [J201703050]
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Background: Numerous studies have shown that prenatal stress (PS) can cause emotional and behavioral abnormalities including depression and depressive-like behaviors in offspring. However, the mechanism underlying the pathophysiology of depression remains largely unknown. In recent years, small metabolic molecules have played an increasingly important role in explaining the pathogenesis of depression. Thus, we detected hippocampal metabolic alteration in rat of depression caused by PS. Methods: To explore the potential molecular markers and pathways that link the metabolic to the pathogenesis of depression, we monitored changes in hippocampus metabolites during the development of depressive-like behaviors in rats exposed to PS via UHPLC-Q-TOF/MS approach. Sucrose preference WA (SPT) was used to screen out the susceptibility rats exposed to PS, open field WA (OFT), forced swimming WA (FST) and tail suspension WA (TST) were used to verify the validity of animal model of depression. Results: A total of 38 differential metabolites were detected in the susceptibility rats exposed to PS compared with that in controls. Most of these differential metabolites were related to Retrograde endocannabinoid signaling, Central carbon metabolism in cancer, Arginine biosynthesis, Choline metabolism in cancer, ABC transporters, Alanine, aspartate and glutamate metabolism pathways. In addition, the results of Spearman correlation analysis indicated that L-aspartate, N-Acetylaspartylglutamate, choline and betaine aldehyde were most associated with depressive-like behaviors. Conclusion: This study demonstrates that hippocampal metabolites in the Alanine, aspartate and glutamate metabolism pathways may play a crucial role in the depressive-like behaviors.
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