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 1day after SPS and then decreased gradually. At the same time, XBP1s appeared and peaked at 4days 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.