title: Homer1 mediates acute stress-induced cognitive deficits in the dorsal hippocampus.
abstract: In recent years, the glutamatergic system has been implicated in the development and treatment of psychiatric disorders. Glutamate signaling is processed by different receptors, including metabotropic glutamate receptors (mGluRs), which in turn interact with the scaffolding protein Homer1 to modulate downstream Ca(2+) signaling. Stress is a major risk factor for the incidence of psychiatric diseases, yet acute stress episodes may have diverging effects on individuals. Cognitive impairments have often been shown to occur after episodes of stress, however the specific role of mGluR5/Homer1 signaling in the interaction of stress and cognition has not yet been elucidated. In this study we show that a single episode of social defeat stress is sufficient to specifically induce cognitive impairments in mice 8 h after the stressor without affecting the animals' locomotion or anxiety levels. We also demonstrate that Homer1b/c levels as well as mGluR5/Homer1b/c interactions in the dorsal hippocampus are reduced up to 8 h after stress. Blockade of mGluR5 during the occurrence of social stress was able to rescue the cognitive impairments. In addition, a specific overexpression of Homer1b/c in the dorsal hippocampus also reversed the behavioral phenotype, indicating that both mGluR5 and Homer1b/c play a crucial role in the mediation of the stress effects. In summary, we could demonstrate that stress induces a cognitive deficit that is likely mediated by mGluR5/Homer1 signaling in the hippocampus. These findings help to reveal the underlying effects of cognitive impairments in patients suffering from stress-related psychiatric disorders.
authors: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors: Klaus V
authors: KV
authors: Wagner
authors: Jakob
authors: J
authors: Hartmann
authors: Katharina
authors: K
authors: Mangold
authors: Xiao-Dong
authors: XD
authors: Wang
authors: Christiana
authors: C
authors: Labermaier
authors: Claudia
authors: C
authors: Liebl
authors: Miriam
authors: M
authors: Wolf
authors: Nils C
authors: NC
authors: Gassen
authors: Florian
authors: F
authors: Holsboer
authors: Theo
authors: T
authors: Rein
authors: Marianne B
authors: MB
authors: Müller
authors: Mathias V
authors: MV
authors: Schmidt
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology* / Q000628:therapy; D003907:Dexamethasone / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D047468:Immunoprecipitation; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology; D012201:Reward; D015398:Signal Transduction / Q000502:physiology; D013028:Space Perception / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications*; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D002352:Carrier Proteins; D018691:Excitatory Amino Acid Antagonists; D005938:Glucocorticoids; C578936:Grm5 protein, mouse; D000072233:Homer Scaffolding Proteins; C000606623:Homer1 protein, mouse; D011725:Pyridines; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; D049452:Green Fluorescent Proteins; D003907:Dexamethasone