Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia
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Stanojlović, Miloš R.Martinović, Jelena
Guševac, Ivana
Grković, Ivana
Mitrović, Nataša Lj.
Zarić, Marina
Horvat, Anica
Drakulić, Dunja R.
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Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17 beta-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 mu g/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of ...the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Box and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes. (C) 2015 Elsevier Ltd. All rights reserved.
Keywords:
Permanent bilateral common carotid arteries occlusion (two-vessel occlusion / 2VO) / Pro-apoptotic signaling / 17 beta-Estradiol (E) / Prefrontal cortexSource:
Neurochemistry International, 2015, 83-84, 1-8Funding / projects:
- Molecular mechanisms of cellular responses on pathological changes in central neuronal system and peripheral organs of mammals (RS-MESTD-Basic Research (BR or ON)-173044)
- Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41014)
DOI: 10.1016/j.neuint.2015.03.002
ISSN: 0197-0186; 1872-9754
PubMed: 25777481
WoS: 000354148700001
Scopus: 2-s2.0-84925677384
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VinčaTY - JOUR AU - Stanojlović, Miloš R. AU - Martinović, Jelena AU - Guševac, Ivana AU - Grković, Ivana AU - Mitrović, Nataša Lj. AU - Zarić, Marina AU - Horvat, Anica AU - Drakulić, Dunja R. PY - 2015 UR - https://vinar.vin.bg.ac.rs/handle/123456789/527 AB - Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17 beta-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 mu g/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Box and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes. (C) 2015 Elsevier Ltd. All rights reserved. T2 - Neurochemistry International T1 - Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia VL - 83-84 SP - 1 EP - 8 DO - 10.1016/j.neuint.2015.03.002 ER -
@article{ author = "Stanojlović, Miloš R. and Martinović, Jelena and Guševac, Ivana and Grković, Ivana and Mitrović, Nataša Lj. and Zarić, Marina and Horvat, Anica and Drakulić, Dunja R.", year = "2015", abstract = "Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17 beta-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 mu g/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Box and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes. (C) 2015 Elsevier Ltd. All rights reserved.", journal = "Neurochemistry International", title = "Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia", volume = "83-84", pages = "1-8", doi = "10.1016/j.neuint.2015.03.002" }
Stanojlović, M. R., Martinović, J., Guševac, I., Grković, I., Mitrović, N. Lj., Zarić, M., Horvat, A.,& Drakulić, D. R.. (2015). Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia. in Neurochemistry International, 83-84, 1-8. https://doi.org/10.1016/j.neuint.2015.03.002
Stanojlović MR, Martinović J, Guševac I, Grković I, Mitrović NL, Zarić M, Horvat A, Drakulić DR. Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia. in Neurochemistry International. 2015;83-84:1-8. doi:10.1016/j.neuint.2015.03.002 .
Stanojlović, Miloš R., Martinović, Jelena, Guševac, Ivana, Grković, Ivana, Mitrović, Nataša Lj., Zarić, Marina, Horvat, Anica, Drakulić, Dunja R., "Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia" in Neurochemistry International, 83-84 (2015):1-8, https://doi.org/10.1016/j.neuint.2015.03.002 . .