Huifang Zhang1, Wei He2, Yinong Huang2, Zhu Zeng1, Xiangdi Yang3, Huimei Huang4, Jun Wen1, Yanjun Cao5, Hongli Sun6. 1. Department of Emergency, Affiliated Children Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 86-710003, PR China. 2. Shaanxi Institute of Pediatric Diseases, Xi'an Key Laboratory of Children's Health and Diseases, Affiliated Children Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 86-710003, PR China. 3. Department of Stomatology, Affiliated Children Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 86-710003, PR China. 4. Department of Nephrology, Affiliated Children Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 86-710003, PR China. 5. Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, Shaanxi, 86-710069, PR China. 6. Shaanxi Institute of Pediatric Diseases, Xi'an Key Laboratory of Children's Health and Diseases, Affiliated Children Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 86-710003, PR China; Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 86-710061, PR China. Electronic address: sunhongligo@yeah.net.
Abstract
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 test (SPT) was used to screen out the susceptibility rats exposed to PS, open field test (OFT), forced swimming test (FST) and tail suspension test (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.
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 test (SPT) was used to screen out the susceptibility rats exposed to PS, open field test (OFT), forced swimming test (FST) and tail suspension test (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.