title: IRE1α-XBP1 Pathway Is Activated Upon Induction of Single-Prolonged Stress in Rat Neurons of the Medial Prefrontal Cortex.
abstract: Endoplasmic reticulum stress (ERS) is associated with many nervous system diseases. IRElα is considered as ERS sensor that, upon activation, initiates the nonconventional splicing of the precursor unspliced form of X-box binding protein 1 (XBP1u) messenger RNA (mRNA) to yield an active transcription factor-XBP1s. The goal of this study is to detect whether there is activation of IRE1α-XBP1 pathway in the medial prefrontal cortex (mPFC) of posttraumatic stress disorder (PTSD) model rats. This study adopted single-prolonged stress (SPS) model. Behavioral functions including anxiety-like behavior, exploration behavior, and spatial memory were assessed by open field test and Morris water maze test. We detected the IRE1α and XBP1 by using methods of double-labeling immunofluorescence, Western blot, and quantitative real-time reverse transcription-PCR (qRT-PCR). We also observed neuronal apoptosis by transferase-mediated dUTP Nick-end-labeling (TUNEL) staining and the expression of caspase-12 by qRT-PCR. Our results showed that the expression of IRE1α, XBP1u, and total XBP1 significantly increased at 1 day after SPS and then decreased gradually. At the same time, XBP1s appeared and peaked at 4 days after SPS, which indicated that IRE1α-XBP1 pathway was activated upon induction of SPS stimulation. We also noted that the mRNA of caspase-12 was upregulated after SPS. Our study preliminarily showed that ERS mediated by IRE1α-XBP1 pathway was closely related to PTSD and it might be a pathogenesis of PTSD.
authors.affiliation: PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018782:Maze Learning; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000071701:Regulatory Factor X Transcription Factors; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; C575026:Ern1 protein, rat; D009097:Multienzyme Complexes; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D053454:Caspase 12