Tags

Type your tag names separated by a space and hit enter

Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK-3β and CREB through PI3-K/Akt pathways.
Eur J Neurosci. 2012 Oct; 36(7):2899-905.EJ

Abstract

Accumulating evidence indicates that resveratrol potently protects against cerebral ischemia damage due to its oxygen free radicals scavenging and antioxidant properties. However, cellular mechanisms that may underlie the neuroprotective effects of resveratrol in brain ischemia are not fully understood yet. This study aimed to investigate the potential association between the neuroprotective effect of resveratrol and the apoptosis/survival signaling pathways, in particular the glycogen synthase kinase 3 (GSK-3β) and cAMP response element-binding protein (CREB) through phosphatidylinositol 3-kinase (PI3-K)-dependent pathway. An experimental model of global cerebral ischemia was induced in rats by the four-vessel occlusion method for 10 min and followed by different periods of reperfusion. Nissl staining indicated extensive neuronal death at 7 days after ischemia/reperfusion. Administration of resveratrol by i.p. injections (30 mg/kg) for 7 days before ischemia significantly attenuated neuronal death. Both GSK-3β and CREB appear to play a critical role in resveratrol neuroprotection through the PI3-K/Akt pathway, as resveratrol pretreatment increased the phosphorylation of Akt, GSK-3β and CREB in 1 h in the CA1 hippocampus after ischemia/reperfusion. Furthermore, administration of LY294002, an inhibitor of PI3-K, compromised the neuroprotective effect of resveratrol and decreased the level of p-Akt, p-GSK-3β and p-CREB after ischemic injury. Taken together, the results suggest that resveratrol protects against delayed neuronal death in the hippocampal CA1 by maintaining the pro-survival states of Akt, GSK-3β and CREB pathways. These data suggest that the neuroprotective effect of resveratrol may be mediated through activation of the PI3-K/Akt signaling pathway, subsequently downregulating expression of GSK-3β and CREB, thereby leading to prevention of neuronal death after brain ischemia in rats.

Authors+Show Affiliations

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil. simaof@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22817531

Citation

Simão, Fabrício, et al. "Resveratrol Prevents CA1 Neurons Against Ischemic Injury By Parallel Modulation of Both GSK-3β and CREB Through PI3-K/Akt Pathways." The European Journal of Neuroscience, vol. 36, no. 7, 2012, pp. 2899-905.
Simão F, Matté A, Pagnussat AS, et al. Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK-3β and CREB through PI3-K/Akt pathways. Eur J Neurosci. 2012;36(7):2899-905.
Simão, F., Matté, A., Pagnussat, A. S., Netto, C. A., & Salbego, C. G. (2012). Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK-3β and CREB through PI3-K/Akt pathways. The European Journal of Neuroscience, 36(7), 2899-905. https://doi.org/10.1111/j.1460-9568.2012.08229.x
Simão F, et al. Resveratrol Prevents CA1 Neurons Against Ischemic Injury By Parallel Modulation of Both GSK-3β and CREB Through PI3-K/Akt Pathways. Eur J Neurosci. 2012;36(7):2899-905. PubMed PMID: 22817531.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK-3β and CREB through PI3-K/Akt pathways. AU - Simão,Fabrício, AU - Matté,Aline, AU - Pagnussat,Aline S, AU - Netto,Carlos A, AU - Salbego,Christianne G, Y1 - 2012/07/22/ PY - 2012/7/24/entrez PY - 2012/7/24/pubmed PY - 2013/2/19/medline SP - 2899 EP - 905 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 36 IS - 7 N2 - Accumulating evidence indicates that resveratrol potently protects against cerebral ischemia damage due to its oxygen free radicals scavenging and antioxidant properties. However, cellular mechanisms that may underlie the neuroprotective effects of resveratrol in brain ischemia are not fully understood yet. This study aimed to investigate the potential association between the neuroprotective effect of resveratrol and the apoptosis/survival signaling pathways, in particular the glycogen synthase kinase 3 (GSK-3β) and cAMP response element-binding protein (CREB) through phosphatidylinositol 3-kinase (PI3-K)-dependent pathway. An experimental model of global cerebral ischemia was induced in rats by the four-vessel occlusion method for 10 min and followed by different periods of reperfusion. Nissl staining indicated extensive neuronal death at 7 days after ischemia/reperfusion. Administration of resveratrol by i.p. injections (30 mg/kg) for 7 days before ischemia significantly attenuated neuronal death. Both GSK-3β and CREB appear to play a critical role in resveratrol neuroprotection through the PI3-K/Akt pathway, as resveratrol pretreatment increased the phosphorylation of Akt, GSK-3β and CREB in 1 h in the CA1 hippocampus after ischemia/reperfusion. Furthermore, administration of LY294002, an inhibitor of PI3-K, compromised the neuroprotective effect of resveratrol and decreased the level of p-Akt, p-GSK-3β and p-CREB after ischemic injury. Taken together, the results suggest that resveratrol protects against delayed neuronal death in the hippocampal CA1 by maintaining the pro-survival states of Akt, GSK-3β and CREB pathways. These data suggest that the neuroprotective effect of resveratrol may be mediated through activation of the PI3-K/Akt signaling pathway, subsequently downregulating expression of GSK-3β and CREB, thereby leading to prevention of neuronal death after brain ischemia in rats. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/22817531/Resveratrol_prevents_CA1_neurons_against_ischemic_injury_by_parallel_modulation_of_both_GSK_3β_and_CREB_through_PI3_K/Akt_pathways_ L2 - https://doi.org/10.1111/j.1460-9568.2012.08229.x DB - PRIME DP - Unbound Medicine ER -