Dataset Information

Protective Effects of Nucleobinding-2 After Cerebral Ischemia Via Modulating Bcl-2/Bax Ratio and Reducing Glial Fibrillary Acid Protein Expression.

ABSTRACT: Introduction:Nucleobinding-2 (NUCB2) or nesfatin-1, a newly identified anorexigenic peptide, has antioxidant, anti-inflammatory, and anti-apoptotic properties. Brain ischemiareperfusion induces irreversible damages, especially in the hippocampus area. However, the therapeutic effects of NUCB2 have not been well investigated in cerebral ischemia. This study was designed for the first time to investigate the protective effects of NUCB2/Nesfatin-1 on the expression of apoptosis-related proteins and reactive astrogliosis level in the CA1 area of hippocampus in an experimental model of transient global cerebral ischemia. Methods:The male Wistar rats were randomly allocated into 4 groups (sham, NUCB2, ischemia-reperfusion, and ischemia-reperfusion+NUCB21) (n =7). The model of cerebral ischemia was prepared by common carotid arteries occlusion for 20 minutes. Nesfatin-1 (20 ?g/kg) and saline (as a vehicle) were injected (intraperitoneally) at the beginning of the reperfusion period. The assessment of the protein expression levels was performed by immunofluorescence and immunohistochemical staining. Results:NUCB2 significantly reduced the Bax and GFAP protein levels in the CA1 area after ischemia (P<0.05). Also, NUCB2 increased Bcl-2 protein level (P<0.05). NUCB2 exerted protective effects against ischemic injury by the inhibition of astrocytes activation as an inflammatory response and decreased neuronal cell apoptosis. Conclusion:The present study provides the possible neuroprotective view of nesfatin-1 in the treatment of ischemia injury model in rat hippocampus.

SUBMITTER: Erfani S

PROVIDER: S-EPMC7149952 | biostudies-literature | 2019 Sep-Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Protective Effects of Nucleobinding-2 After Cerebral Ischemia Via Modulating Bcl-2/Bax Ratio and Reducing Glial Fibrillary Acid Protein Expression.

Erfani Sohaila S Moghimi Ali A Aboutaleb Nahid N Khaksari Mehdi M

Basic and clinical neuroscience 20190901 5

<h4>Introduction</h4>Nucleobinding-2 (NUCB2) or nesfatin-1, a newly identified anorexigenic peptide, has antioxidant, anti-inflammatory, and anti-apoptotic properties. Brain ischemiareperfusion induces irreversible damages, especially in the hippocampus area. However, the therapeutic effects of NUCB2 have not been well investigated in cerebral ischemia. This study was designed for the first time to investigate the protective effects of NUCB2/Nesfatin-1 on the expression of apoptosis-related prot ...[more]

PMID: 32284834

Similar Datasets

Project description:PURPOSE: Apoptosis is known to play a key role in cell death after retinal ischemia. However, little is known about the kinetics of the signaling pathways involved and their contribution to this process. The aim of this study was to determine whether changes in the expression of molecules in the mitochondrial apoptotic pathway might explain the progression of retinal damage following ischemia/reperfusion. METHODS: Retinal ischemia was induced by elevating intraocular pressure in the vitreous cavity to 150 mmHg for a period of 60 min. At time 0, 3 h (early phase), and 24 h (late phase) after reperfusion, the retinas were harvested and modifications in the expression of Bax, Bak, Bcl-2, and Bcl-x(L) as well as caspase-3 and -7, were examined by qPCR and, in some cases, by western blot. RESULTS: qPCR analysis performed at the early phase after ischemia revealed a time dependent decrease in Bax, Bak, and Bcl-x(L) and no alteration in Bcl-2 mRNA expression in response to retinal ischemia. At the protein level, proapoptotic Bax and Bak were not modulated while Bcl-2 and Bcl-x(L) were significantly upregulated. At this stage, the Bax per Bcl-2 and Bax:Bcl-x(L) ratios were not modified. At the late phase of recovery, Bax and Bcl-x(L) mRNAs were downregulated while Bak was increased. Increased Bax:Bcl-2 and Bax:Bcl-x(L) ratios at both the mRNA and protein levels were observed 24 h after the ischemic insult. Analysis of caspases associated with mitochondria-mediated apoptosis revealed a specific increase in the expression of caspase-3 in the ischemic retinas 24 h after reperfusion, and a decrease in the expression of caspase-7. CONCLUSIONS: This study revealed that Bcl-2-related family members were differently regulated in the early and late phases after an ischemic insult. We showed that the Bax:Bcl-2 and Bax:Bcl-x(L) balances were not affected in the initial phases, but the Bax:Bcl-x(L) ratio shifted toward apoptosis during the late phase of recovery. This shift was reinforced by caspase-3 upregulation.

Project description:Background Blood-based biomarkers for Alzheimer’s disease (AD) might facilitate identification of participants for clinical trials targeting amyloid beta (Abeta) accumulation, and aid in AD diagnostics. We examined the potential of plasma markers Abeta(1-42/1-40), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) to identify cerebral amyloidosis and/or disease severity. Methods We included individuals with a positive (n?=?176: 63?±?7?years, 87 (49%) females) or negative (n?=?76: 61?±?9?years, 27 (36%) females) amyloid PET status, with syndrome diagnosis subjective cognitive decline (18 PET+, 25 PET?), mild cognitive impairment (26 PET+, 24 PET?), or AD-dementia (132 PET+). Plasma Abeta(1-42/1-40), GFAP, and NfL were measured by Simoa. We applied two-way ANOVA adjusted for age and sex to investigate the associations of the plasma markers with amyloid PET status and syndrome diagnosis; logistic regression analysis with Wald’s backward selection to identify an optimal panel that identifies amyloid PET positivity; age, sex, and education-adjusted linear regression analysis to investigate associations between the plasma markers and neuropsychological test performance; and Spearman’s correlation analysis to investigate associations between the plasma markers and medial temporal lobe atrophy (MTA). Results Abeta(1-42/1-40) and GFAP independently associated with amyloid PET status (p?=?0.009 and p?<?0.001 respectively), and GFAP and NfL independently associated with syndrome diagnosis (p?=?0.001 and p?=?0.048 respectively). The optimal panel identifying a positive amyloid status included Abeta(1-42/1-40) and GFAP, alongside age and APOE (AUC?=?88% (95% CI 83–93%), 82% sensitivity, 86% specificity), while excluding NfL and sex. GFAP and NfL robustly associated with cognitive performance on global cognition and all major cognitive domains (GFAP: range standardized ? (s?)?=???0.40 to ??0.26; NfL: range s??=???0.35 to ??0.18; all: p?<?0.002), whereas Abeta(1-42/1-40) associated with global cognition, memory, attention, and executive functioning (range s??=?0.22 – 0.11; all: p?<?0.05) but not language. GFAP and NfL showed moderate positive correlations with MTA (both: Spearman’s rho>?0.33, p?<?0.001). Abeta(1-42/1-40) showed a moderate negative correlation with MTA (Spearman’s rho?=???0.24, p?=?0.001). Discussion and conclusions Combination of plasma Abeta(1-42/1-40) and GFAP provides a valuable tool for the identification of amyloid PET status. Furthermore, plasma GFAP and NfL associate with various disease severity measures suggesting potential for disease monitoring.

Dataset Information

Protective Effects of Nucleobinding-2 After Cerebral Ischemia Via Modulating Bcl-2/Bax Ratio and Reducing Glial Fibrillary Acid Protein Expression.

Publications

Protective Effects of Nucleobinding-2 After Cerebral Ischemia Via Modulating Bcl-2/Bax Ratio and Reducing Glial Fibrillary Acid Protein Expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets