title: Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression.
abstract: Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Jia
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ding
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Shang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Zhong-Mei
authors.initials: ZM
authors.lastname: Zou
mesh_terms: D000818:Animals; D003863:Depression / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D012372:ROC Curve; D051381:Rats; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics / Q000378:metabolism