title: Single-prolonged stress activates the transcription factor ATF6α branch of the unfolded protein response in rat neurons of dorsal raphe nucleus.
abstract: In our previous studies, we have found that endoplasmic reticulum (ER) stress is associated with post-traumatic stress disorder (PTSD), however, the activation of ER stress sensors in PTSD remains unclear. ATF6 alpha (ATF6α) is an ER-membrane-bound transcription factor and functions as a critical sensor and regulator of ER stress in mammalian cells. The goal of this study is to detect whether there is activation of the transcription factor ATF6α branch of the unfolded protein response in the dorsal raphe nucleus neurons of the rats exposed to single-prolonged stress (SPS), which is a model employed extensively in PTSD study. Our results have demonstrated that SPS activated the ER transmembrane protein ATF6α via its cleavage; and induced the up-regulation of the downstream targets of ATF6α, the mRNA of XBP1 and GRP94. To the best of our knowledge, this is the first study to investigate the relationship between the ATF6α pathways and PTSD, and our results show that SPS activates the ATF6α branch of the ER stress response, which may be contributed to the pathogenesis of PTSD.
authors.affiliation: Laboratory of Post-Traumatic Stress Disorder, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, 92 North 2nd Road, Shenyang, 110001, Liaoning Province, People's Republic of China.
authors.forename: Juhua
authors.initials: J
authors.lastname: Xie
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Shi
mesh_terms: D051702:Activating Transcription Factor 6 / Q000502:physiology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D065847:Dorsal Raphe Nucleus / Q000473:pathology; D015870:Gene Expression; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D017208:Rats, Wistar; D000071701:Regulatory Factor X Transcription Factors; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000473:pathology; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response; D000071717:X-Box Binding Protein 1
chemical_list: D051702:Activating Transcription Factor 6; C497113:Atf6 protein, rat; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat; C053387:endoplasmin