title: Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.
abstract: Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.
authors.affiliation: Department of Pharmacology, Anhui Xinhua University, Hefei, Anhui 230088, P.R. China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Yin
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Yu-Chan
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Wei-Zu
authors.initials: WZ
authors.lastname: Li
mesh_terms: D000818:Animals; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007858:Learning; D008297:Male; D008568:Memory; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D009419:Nerve Tissue Proteins