Tags

Type your tag names separated by a space and hit enter

Protection against Experimental Stroke by Ganglioside GM1 Is Associated with the Inhibition of Autophagy.
PLoS One. 2016; 11(1):e0144219.Plos

Abstract

Ganglioside GM1, which is particularly abundant in the central nervous system (CNS), is closely associated with the protection against several CNS disorders. However, controversial findings have been reported on the role of GM1 following ischemic stroke. In the present study, using a rat middle cerebral artery occlusion (MCAO) model, we investigated whether GM1 can protect against ischemic brain injury and whether it targets the autophagy pathway. GM1 was delivered to Sprague-Dawley male rats at 3 doses (25 mg/kg, 50 mg/kg, 100 mg/kg) by intraperitoneal injection soon after reperfusion and then once daily for 2 days. The same volume of saline was given as a control. Tat-Beclin-1, a specific autophagy inducer, was administered by intraperitoneal injection at 24 and 48 hours post-MCAO. Infarction volume, mortality and neurological function were assessed at 72 hours after ischemic insult. Immunofluorescence and Western blotting were performed to determine the expression of autophagy-related proteins P62, LC3 and Beclin-1 in the penumbra area. No significant changes in mortality and physiological variables (heart rate, blood glucose levels and arterial blood gases) were observed between the different groups. However, MCAO resulted in enhanced conversion of LC3-I into LC3-II, P62 degradation, high levels of Beclin-1, a large area infarction (26.3±3.6%) and serious neurobehavioral deficits. GM1 (50 mg/kg) treatment significantly reduced the autophagy activation, neurobehavioral dysfunctions, and infarction volume (from 26.3% to 19.5%) without causing significant adverse side effects. However, this biological function could be abolished by Tat-Beclin-1.

IN CONCLUSION

GM1 demonstrated safe and robust neuroprotective effects that are associated with the inhibition of autophagy following experimental stroke.

Authors+Show Affiliations

Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.Department of Anatomy, Heze Medical College, Shandong, China.Osteopathic Medicine, Des Moines University, Des Moines, Iowa, United States of America.Department of Neurology, People's hospital of Deyang City, Sichuan, China.Department of Anatomy & Histology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.Department of Anatomy & Histology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Pub Type(s)

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

Language

eng

PubMed ID

26751695

Citation

Li, Li, et al. "Protection Against Experimental Stroke By Ganglioside GM1 Is Associated With the Inhibition of Autophagy." PloS One, vol. 11, no. 1, 2016, pp. e0144219.
Li L, Tian J, Long MK, et al. Protection against Experimental Stroke by Ganglioside GM1 Is Associated with the Inhibition of Autophagy. PLoS ONE. 2016;11(1):e0144219.
Li, L., Tian, J., Long, M. K., Chen, Y., Lu, J., Zhou, C., & Wang, T. (2016). Protection against Experimental Stroke by Ganglioside GM1 Is Associated with the Inhibition of Autophagy. PloS One, 11(1), e0144219. https://doi.org/10.1371/journal.pone.0144219
Li L, et al. Protection Against Experimental Stroke By Ganglioside GM1 Is Associated With the Inhibition of Autophagy. PLoS ONE. 2016;11(1):e0144219. PubMed PMID: 26751695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protection against Experimental Stroke by Ganglioside GM1 Is Associated with the Inhibition of Autophagy. AU - Li,Li, AU - Tian,Jinghua, AU - Long,Mitchell King-Wei, AU - Chen,Yong, AU - Lu,Jianfei, AU - Zhou,Changman, AU - Wang,Tianlong, Y1 - 2016/01/11/ PY - 2015/03/11/received PY - 2015/11/03/accepted PY - 2016/1/12/entrez PY - 2016/1/12/pubmed PY - 2016/6/30/medline SP - e0144219 EP - e0144219 JF - PloS one JO - PLoS ONE VL - 11 IS - 1 N2 - UNLABELLED: Ganglioside GM1, which is particularly abundant in the central nervous system (CNS), is closely associated with the protection against several CNS disorders. However, controversial findings have been reported on the role of GM1 following ischemic stroke. In the present study, using a rat middle cerebral artery occlusion (MCAO) model, we investigated whether GM1 can protect against ischemic brain injury and whether it targets the autophagy pathway. GM1 was delivered to Sprague-Dawley male rats at 3 doses (25 mg/kg, 50 mg/kg, 100 mg/kg) by intraperitoneal injection soon after reperfusion and then once daily for 2 days. The same volume of saline was given as a control. Tat-Beclin-1, a specific autophagy inducer, was administered by intraperitoneal injection at 24 and 48 hours post-MCAO. Infarction volume, mortality and neurological function were assessed at 72 hours after ischemic insult. Immunofluorescence and Western blotting were performed to determine the expression of autophagy-related proteins P62, LC3 and Beclin-1 in the penumbra area. No significant changes in mortality and physiological variables (heart rate, blood glucose levels and arterial blood gases) were observed between the different groups. However, MCAO resulted in enhanced conversion of LC3-I into LC3-II, P62 degradation, high levels of Beclin-1, a large area infarction (26.3±3.6%) and serious neurobehavioral deficits. GM1 (50 mg/kg) treatment significantly reduced the autophagy activation, neurobehavioral dysfunctions, and infarction volume (from 26.3% to 19.5%) without causing significant adverse side effects. However, this biological function could be abolished by Tat-Beclin-1. IN CONCLUSION: GM1 demonstrated safe and robust neuroprotective effects that are associated with the inhibition of autophagy following experimental stroke. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26751695/Protection_against_Experimental_Stroke_by_Ganglioside_GM1_Is_Associated_with_the_Inhibition_of_Autophagy_ L2 - http://dx.plos.org/10.1371/journal.pone.0144219 DB - PRIME DP - Unbound Medicine ER -