title: Chronic combined stress induces selective and long-lasting inflammatory response evoked by changes in corticosterone accumulation and signaling in rat hippocampus.
abstract: Hippocampus is believed to be selectively vulnerable to stress. We hypothesized that this phenomenon may be mediated by relatively high vulnerability to neuroinflammation related to impairments of local glucocorticoid metabolism and signaling. We have evaluated inflammatory responses induced by acute or chronic combined stress in the cerebral cortex and hippocampus as well as circulating and brain corticosterone (CS) levels as well as expression of corticosterone target genes. The hippocampus showed higher stress-induced expression of the proinflammatory cytokine IL-1β as compared to the cerebral cortex. A month after the termination of the chronic stress, IL-1β mRNA in the cerebral cortex reached control level, while in the hippocampus it remained significantly increased. Under chronic stress, the maladaptive inflammatory response in hippocampus was accompanied by a significant increase in local CS levels, as compared to cerebral cortex. Under acute stress, the increased CS level induced changes in CS-regulated genes expression (CRF and IGF1), while this phenomenon was not observed after chronic stress. Thus, the hippocampus appears to be more vulnerable to stress-induced inflammation as compared to the neocortex and demonstrates persistent inflammatory response induced by chronic stress. Stress-induced maladaptive inflammatory response is associated with a selective increase in hippocampal CS accumulation and changes in CS signaling.
authors.affiliation: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Piskunov
authors.affiliation: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Stepanichev
authors.affiliation: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Tishkina
authors.affiliation: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia.
authors.forename: Margarita
authors.initials: M
authors.lastname: Novikova
authors.affiliation: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Levshina
authors.affiliation: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia. nata_gul@mail.ru.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gulyaeva
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D003345:Corticosterone
keywords: Corticosterone; Glucocorticoid; Hippocampus; Neuroinflammation; Stress