Altered Expression of Endoplasmic Reticulum Stress Associated Genes in Hippocampus of Learned Helpless Rats: Relevance to Depression Pathophysiology

Frontiers in Pharmacology
Matthew A Timberlake, Yogesh Dwivedi

Abstract

The unfolded protein response (UPR) is an evolutionarily conserved defensive mechanism that is used by cells to correct misfolded proteins that accumulate in the endoplasmic reticulum. These proteins are misfolded as a result of physical stress on a cell and initiate a host of downstream effects that govern processes ranging from inflammation to apoptosis. To examine whether UPR system plays a role in depression, we examined the expression of genes that are part of the three different pathways for UPR activation, namely GRP78, GRP94, ATF6, XBP-1, ATF4, and CHOP using an animal model system that distinguishes vulnerability (learned helpless, LH) from resistance (non-learned helpless, NLH) to develop depression. Rats were exposed to inescapable shock on days 1 and 7 and were tested for escape latency on day 14. Rats not given shock but tested for escape latency were used as tested control (TC). Plasma corticosterone (CORT) levels were measured. Expression levels of various UPR associated genes were determined in hippocampus using qPCR. We found that the CORT level was higher in LH rats compared with TC and NLH rats. Expression of GRP78, GRP94, ATF6, and XBP-1 were significantly upregulated in LH rats compared with TC or NLH rats,...Continue Reading

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Citations

Nov 7, 2016·Apoptosis : an International Journal on Programmed Cell Death·Chunchen XiangFang Han
Apr 29, 2018·Molecular Neurobiology·Birgit LudwigYogesh Dwivedi
Oct 2, 2019·Current Neuropharmacology·Kaipuzha Venu AthiraSumana Chakravarty
Nov 9, 2019·Molecular Medicine Reports·Jiaxin MaoZhongze Lou
Jan 17, 2019·Neural Plasticity·Amanda CriderAnilkumar Pillai
Oct 1, 2020·International Journal of Molecular Sciences·Mikhail V VoroninSergei B Seredenin
Feb 26, 2021·Drug Discoveries & Therapeutics·Megumi FurukawaYasuo Watanabe
Nov 14, 2017·Neuropharmacology·Luis E Santos, Sergio T Ferreira
Jun 3, 2021·Cells·Jesús BurilloCarlos Guillén

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Methods Mentioned

BETA
protein folding
electrophoresis
PCR

Software Mentioned

Statistical Package for the Social Sciences ( SPSS )

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis