title: Expression patterns of c-Fos early gene and phosphorylated ERK in the rat brain following 1-h immobilization stress: concomitant changes induced in association with stress-related sleep rebound.
abstract: An immobilization stress (IS) of 1 h applied at the beginning of the dark phase is followed by a sleep rebound. During the restraint, serotonin released by the dorsal raphe nucleus within the arcuate area stimulates the availability of corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39). Three hours after the restraint, CLIP, through its hypnogenic properties, contributes to the sleep rebound that follows the IS. Here, we immunohistochemically evaluated protein expression of the immediate early gene, c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in hypothalamic (preoptic area [POA], paraventricular nucleus [PVN], arcuate nucleus [ARC]) and brain stem (dorsal raphe [DR], locus coeruleus [LC]) nuclei involved in the acute response to stress and the subsequent stress-related sleep rebound (recovery period). Immediately after the 1-h restraint, c-Fos and p-ERK expression increased in all structures studied, particularly in PVN and LC. Three hours later, the number of p-ERK- and c-Fos-positive neurons was reduced in PVN and LC (p < 0.001) as well as in DR (p < 0.01) compared to control animals. In contrast, both c-Fos and p-ERK expression in POA neurons (p < 0.01) and c-Fos expression in ARC neurons (p < 0.001) were increased 3 h after the IS. The marked activation observed in PVN and LC nucleus immediately after the IS confirms that these structures are clearly reactive to stress. However, the high activity observed in POA and ARC neurons during the recovery period, not described to date, highlights the particular part played by these structures in the stress-related sleep rebound. An unbalance in the above processes may contribute to pathological outcomes, such as anxiety and depression.
authors.affiliation: Functional Neuroanatomy Laboratory, Physiology Department and Neuroscience Research Center, Faculty of Medicine, Shahid Beheshti Medical Sciences University, Evin, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Keshavarzy
authors.forename: Chantal
authors.initials: C
authors.lastname: Bonnet
authors.forename: Gila
authors.initials: G
authors.lastname: Behzadi
authors.forename: Gila
authors.initials: G
authors.lastname: Bezhadi
authors.forename: Raymond
authors.initials: R
authors.lastname: Cespuglio
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D065847:Dorsal Raphe Nucleus / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D017781:Genes, Immediate-Early; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010766:Phosphorylation; D011301:Preoptic Area / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000523:psychology*; D012890:Sleep; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D048049:Extracellular Signal-Regulated MAP Kinases