Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus
Апстракт
Stress-related glucocorticoids and glutamate release has been implicated in depression. Glutamate neurotoxicity is mediated, in part, by the production of nitric oxide via nitric oxide synthase (NOS) isoforms and mitochondrial damage. We previously reported that chronic social isolation stress triggers proapoptotic signaling in the rat prefrontal cortex, but not in the hippocampus. Given that the hippocampus is highly sensitive to stress, we examined signaling cascades underlying the hippocampal cellular protection through the NOS pathway, antioxidant capacity and heat shock protein (Hsp) expression. We investigated neuronal (nNOS) and inducible (iNOS) protein levels, subcellular protein distributions of nuclear factor-kappa B (NF-kappa B), CuZnSOD and MnSOD activity, reduced glutathione (GSH), stress-inducible Hsp70 (Hsp70i) protein expression and serum corticosterone (CORT) levels of rats exposed to 21 days of chronic social isolation, an animal model of depression, alone or in combi...nation with 2 h of acute immobilization or cold stress (combined stress). Both acute stressors elevated CORT, with lesser magnitude increase in chronically isolated rats exposed to novel acute stress as compared to acute stressors alone, indicating compromised HPA axis activity. Acute cold decreased nuclear CuZnSOD activity and stimulated NF-kappa B nuclear translocation. Chronic social isolation resulted in no activation of NF-kappa B, but led to decreased GSH, iNOS and increased nNOS and Hsp70i levels, alterations that remained following combined stressors. Decreased mitochondrial MnSOD activity after combined stressors suggests compromised detoxifying capacity. These data indicate that Hsp70i upregulation may provide hippocampal cellular protection against chronic social isolation stress mediated by downregulation of iNOS protein expression through suppression of NF-kappa B activation.
Кључне речи:
Chronic social isolation / Hippocampus / Hsp70i / NF-kappa B / Nitric oxide synthasesИзвор:
Journal of Neural Transmission, 2014, 121, 1, 3-14Финансирање / пројекти:
- Молекуларни механизми патофизиолошких промена у ћелијама централног нервног система и периферног ткива код сисара (RS-MESTD-Basic Research (BR or ON)-173044)
DOI: 10.1007/s00702-013-1066-1
ISSN: 0300-9564; 1435-1463
PubMed: 23851625
WoS: 000329239500002
Scopus: 2-s2.0-84892672746
Институција/група
VinčaTY - JOUR AU - Martinović, Jelena AU - Bernardi, Rick E. AU - Filipović, Dragana PY - 2014 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5826 AB - Stress-related glucocorticoids and glutamate release has been implicated in depression. Glutamate neurotoxicity is mediated, in part, by the production of nitric oxide via nitric oxide synthase (NOS) isoforms and mitochondrial damage. We previously reported that chronic social isolation stress triggers proapoptotic signaling in the rat prefrontal cortex, but not in the hippocampus. Given that the hippocampus is highly sensitive to stress, we examined signaling cascades underlying the hippocampal cellular protection through the NOS pathway, antioxidant capacity and heat shock protein (Hsp) expression. We investigated neuronal (nNOS) and inducible (iNOS) protein levels, subcellular protein distributions of nuclear factor-kappa B (NF-kappa B), CuZnSOD and MnSOD activity, reduced glutathione (GSH), stress-inducible Hsp70 (Hsp70i) protein expression and serum corticosterone (CORT) levels of rats exposed to 21 days of chronic social isolation, an animal model of depression, alone or in combination with 2 h of acute immobilization or cold stress (combined stress). Both acute stressors elevated CORT, with lesser magnitude increase in chronically isolated rats exposed to novel acute stress as compared to acute stressors alone, indicating compromised HPA axis activity. Acute cold decreased nuclear CuZnSOD activity and stimulated NF-kappa B nuclear translocation. Chronic social isolation resulted in no activation of NF-kappa B, but led to decreased GSH, iNOS and increased nNOS and Hsp70i levels, alterations that remained following combined stressors. Decreased mitochondrial MnSOD activity after combined stressors suggests compromised detoxifying capacity. These data indicate that Hsp70i upregulation may provide hippocampal cellular protection against chronic social isolation stress mediated by downregulation of iNOS protein expression through suppression of NF-kappa B activation. T2 - Journal of Neural Transmission T1 - Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus VL - 121 IS - 1 SP - 3 EP - 14 DO - 10.1007/s00702-013-1066-1 ER -
@article{ author = "Martinović, Jelena and Bernardi, Rick E. and Filipović, Dragana", year = "2014", abstract = "Stress-related glucocorticoids and glutamate release has been implicated in depression. Glutamate neurotoxicity is mediated, in part, by the production of nitric oxide via nitric oxide synthase (NOS) isoforms and mitochondrial damage. We previously reported that chronic social isolation stress triggers proapoptotic signaling in the rat prefrontal cortex, but not in the hippocampus. Given that the hippocampus is highly sensitive to stress, we examined signaling cascades underlying the hippocampal cellular protection through the NOS pathway, antioxidant capacity and heat shock protein (Hsp) expression. We investigated neuronal (nNOS) and inducible (iNOS) protein levels, subcellular protein distributions of nuclear factor-kappa B (NF-kappa B), CuZnSOD and MnSOD activity, reduced glutathione (GSH), stress-inducible Hsp70 (Hsp70i) protein expression and serum corticosterone (CORT) levels of rats exposed to 21 days of chronic social isolation, an animal model of depression, alone or in combination with 2 h of acute immobilization or cold stress (combined stress). Both acute stressors elevated CORT, with lesser magnitude increase in chronically isolated rats exposed to novel acute stress as compared to acute stressors alone, indicating compromised HPA axis activity. Acute cold decreased nuclear CuZnSOD activity and stimulated NF-kappa B nuclear translocation. Chronic social isolation resulted in no activation of NF-kappa B, but led to decreased GSH, iNOS and increased nNOS and Hsp70i levels, alterations that remained following combined stressors. Decreased mitochondrial MnSOD activity after combined stressors suggests compromised detoxifying capacity. These data indicate that Hsp70i upregulation may provide hippocampal cellular protection against chronic social isolation stress mediated by downregulation of iNOS protein expression through suppression of NF-kappa B activation.", journal = "Journal of Neural Transmission", title = "Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus", volume = "121", number = "1", pages = "3-14", doi = "10.1007/s00702-013-1066-1" }
Martinović, J., Bernardi, R. E.,& Filipović, D.. (2014). Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus. in Journal of Neural Transmission, 121(1), 3-14. https://doi.org/10.1007/s00702-013-1066-1
Martinović J, Bernardi RE, Filipović D. Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus. in Journal of Neural Transmission. 2014;121(1):3-14. doi:10.1007/s00702-013-1066-1 .
Martinović, Jelena, Bernardi, Rick E., Filipović, Dragana, "Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus" in Journal of Neural Transmission, 121, no. 1 (2014):3-14, https://doi.org/10.1007/s00702-013-1066-1 . .