Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Oct 15:211:102-117.
doi: 10.1016/j.lfs.2018.09.016. Epub 2018 Sep 7.

iTRAQ-based proteomics suggests LRP6, NPY and NPY2R perturbation in the hippocampus involved in CSDS may induce resilience and susceptibility

Yong He  1 , Wei Li  2 , Yu Tian  3 , Xi Chen  3 , Ke Cheng  2 , Ke Xu  3 , Chenmeng Li  4 , Haiyang Wang  5 , Chaohua Qu  3 , Chunlian Wang  6 , Pengfei Li  5 , Huanxin Chen  7 , Peng Xie  8
Affiliations

iTRAQ-based proteomics suggests LRP6, NPY and NPY2R perturbation in the hippocampus involved in CSDS may induce resilience and susceptibility

Yong He et al. Life Sci. .

Abstract

Aims: Although decades of research have revealed numerous molecular abnormalities in the hippocampus associated with depression, the different mechanisms involved in the susceptibility and resilience of mice to chronic social defeat stress (CSDS)-induced depression remain poorly understand. Through the social defeat model, we can study the differences in molecular changes between the susceptible and resilient mice.

Main methods: We used a proteomic-based platform to compare hippocampal proteins in CSDS mice with those in control mice. Differentially expressed proteins were identified through isobaric tags for relative and absolute quantitation (iTRAQ) combined with LC-MS/MS. We then analyzed the results by ingenuity pathway analysis (IPA) and verified five proteins by western blotting.

Key findings: Mice were exposed to 10 days of CSDS, which successfully induced stress-susceptible and -resilient phenotypes. 161 and 134 proteins were significantly differentially expressed in the susceptible and resilient groups, respectively, compared with the levels in the control group. The Rac signaling and the GABA receptors signaling pathways were the common top-ranking pathways. We found that low-density lipoprotein receptor-related protein 6 (LRP6) was upregulated in resilient mice and neuropeptide Y (NPY) was downregulated in susceptible mice compared with the levels in control mice. Moreover, neuropeptide Y receptor type 2 (NPY2R) protein expression in susceptible mice was downregulated compared with that in the resilient group.

Significance: Our findings in the three groups potentially reveal the differences in molecular mechanisms underlying depression between susceptible and resilient mice. The results provide insight into molecular abnormalities of the hippocampus in CSDS mice and some potential drug targets for treating depression.

Keywords: Chronic social defeat stress; Hippocampus; Major depressive disorder; Proteomics; iTRAQ.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Substances

LinkOut - more resources