title: Effects of 5-h multimodal stress on the molecules and pathways involved in dendritic morphology and cognitive function.
abstract: Stress induces cognitive impairments, which are likely related to the damaged dendritic morphology in the brain. Treatments for stress-induced impairments remain limited because the molecules and pathways underlying these impairments are unknown. Therefore, the aim of this study was to find the potential molecules and pathways related to damage of the dendritic morphology induced by stress. To do this, we detected gene expression, constructed a protein-protein interaction (PPI) network, and analyzed the molecular pathways in the brains of mice exposed to 5-h multimodal stress. The results showed that stress increased plasma corticosterone concentration, decreased cognitive function, damaged dendritic morphologies, and altered APBB1, CLSTN1, KCNA4, NOTCH3, PLAU, RPS6KA1, SYP, TGFB1, KCNA1, NTRK3, and SNCA expression in the brains of mice. Further analyses found that the abnormal expressions of CLSTN1, PLAU, NOTCH3, and TGFB1 induced by stress were related to alterations in the dendritic morphology. These four genes demonstrated interactions with 55 other genes, and configured a closed PPI network. Molecular pathway analysis use the Database for Annotation, Visualization, and Integrated Discovery (DAVID), specifically the gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG), each identified three pathways that were significantly enriched in the gene list of the PPI network, with genes belonging to the Notch and transforming growth factor-beta (TGF-B) signaling pathways being the most enriched. Our results suggest that TGFB1, PLAU, NOTCH3, and CLSTN1 may be related to the alterations in dendritic morphology induced by stress, and imply that the Notch and TGF-B signaling pathways may be involved.
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China. Electronic address: cxr916@163.com.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Xiuliang
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Tongxing
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Ruishang
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Bo
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Shengqi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China. Electronic address: zhouwx@bmi.ac.cn.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood*; D003712:Dendrites / Q000473:pathology*; D015870:Gene Expression / Q000502:physiology*; D063990:Gene Ontology; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D060066:Protein Interaction Maps / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D003345:Corticosterone
keywords: Cognition; Corticosterone; Dendrite; Gene expression; Hours-long multimodal stress