title: Investigations on GSK-3β/NF-kB signaling in stress and stress adaptive behavior in electric foot shock subjected mice.
abstract: The present study was designed to explore the role of GSK-3β and NF-kB signaling in electric foot shock-induced stress and stress adaptation. Mice were subjected to foot shocks of 0.5mA intensity and 1s duration of 1h to produce acute stress. Animals were exposed to the same stressor for 5 days to induce stress adaptation. The behavioral alterations were assessed using the actophotometer, hole board, open field and social interaction tests. The serum corticosterone levels were assessed as a marker of the HPA axis. The levels of total GSK-3β, p-GSK-3β-S9 and p-NF-kB were determined in the hippocampus, frontal cortex and amygdala. Acute electric foot shock stress produced behavioral and biochemical changes; decreased the levels of p-GSK-3β-S9, produced no change in total GSK-3β levels and increased p-NF-kB levels in the brain. However, repeated exposure of foot shock stress restored the behavioral and biochemical changes along with normalization of p-GSK-3β-S9 and p-NF-kB levels. Administration of AR-A01, a selective GSK-3β inhibitor, or diethyldithiocarbamic acid (DDTC), a selective NF-kB inhibitor, diminished acute stress-induced behavioral and biochemical changes. Furthermore, AR-A014418 normalized acute stress-induced alterations in p-GSK-3β-S9 and p-NF-kB levels, however, DDTC selectively restored NF-kB levels without any change in p-GSK-3β-S9 levels. It probably suggests that NF-kB is a downstream mediator of the GSK-3 signaling cascade. It may conclude that acute stress associated decrease in p-GSK-3β-S9 and increase in p-NF-kB levels in the brain contribute in the development of behavioral and biochemical alterations and normalization of GSK-3β/NF-kB signaling may contribute in stress adaptive behavior in response to repeated electric foot shock-subjected mice.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India. Electronic address: anjubali.123@gmail.com.
authors.forename: Anjana
authors.initials: A
authors.lastname: Bali
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India. Electronic address: amteshwarjaggi@yahoo.co.in.
authors.forename: Amteshwar Singh
authors.initials: AS
authors.lastname: Jaggi
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004050:Ditiocarb / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D007398:Interpersonal Relations; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D013844:Thiazoles / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D013844:Thiazoles; C479831:N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea; D014508:Urea; D004050:Ditiocarb; D000071679:Glycogen Synthase Kinase 3 beta; D003345:Corticosterone
keywords: Behavior; Corticosterone; Electric foot shock; GSK-3β; NF-kB; Stress adaptation