title: PERK signalling pathway mediates single prolonged stress-induced dysfunction of medial prefrontal cortex neurons.
abstract: Post-traumatic stress disorder (PTSD) is characterized with abnormal learning and memory. Impairments in learning and memory are closely associated with apoptosis in the medial prefrontal cortex (mPFC). We previously examined the endoplasmic reticulum (ER) stress was involved in the apoptosis in the mPFC of PTSD. The PERK pathway plays the important role in the ER stress-induced apoptosis. The aim of the present study was to explore the role of PERK pathway in neuronal apoptosis in the mPFC of rat models of PTSD. We used the single prolonged stress (SPS) to mimic PTSD in rats and studied the effects of the PERK pathway in mPFC. Learning and memory behavior were examined by Morris water maze and novel object recognition tests. Apoptosis in mPFC was detected by TUNEL staining. Our results showed decreased learning memory and increased apoptosis of mPFC neurons in rats exposed to SPS. SPS exposure upregulate mRNA expressions of PERK, p-PERK, eIF2α, p-eIF2α, nuclear ATF4 and C/EBP-homologous protein (CHOP) in mPFC neurons, but the protein levels of these molecules showed difference in magnitude and time course. GSK2606414 (an antagonist of PERK) treatment successfully reversed the above changes. These results suggested that the PERK pathway mediated SPS-induced neural apoptosis in the mPFC. These findings will be helpful in understanding mPFC-related pathogenesis of PTSD.
authors.affiliation: PTSD Lab, Department of Histo-Embryology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wen
authors.affiliation: PTSD Lab, Department of Histo-Embryology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.affiliation: PTSD Lab, Department of Histo-Embryology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China.
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: PTSD Lab, Department of Histo-Embryology, Basic Medical Sciences College, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China. fhan@cmu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D053454:Caspase 12 / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D051701:Activating Transcription Factor 4; D000225:Adenine; D053454:Caspase 12; D015852:Eukaryotic Initiation Factor-2; D007211:Indoles; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C576403:7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine; C497110:Atf4 protein, rat
keywords: Apoptosis; Medical prefrontal cortex; PERK; Post-traumatic stress disorder; eIF2a