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J.R. Liu, C. Baek, X.H. Han, P. Shoureshi, S.G. Soriano 

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Presentation on theme: "J.R. Liu, C. Baek, X.H. Han, P. Shoureshi, S.G. Soriano "— Presentation transcript:

1 Role of glycogen synthase kinase-3β in ketamine-induced developmental neuroapoptosis in rats 
J.R. Liu, C. Baek, X.H. Han, P. Shoureshi, S.G. Soriano  British Journal of Anaesthesia  Volume 110, Pages i3-i9 (June 2013) DOI: /bja/aet057 Copyright © 2013 The Author(s) Terms and Conditions

2 Fig 1 Ketamine temporally increased caspase-3 activation and decreased phosphorylation of GSK-3β. Five groups received i.p. injections (10 ml kg−1) of either ketamine (2 mg ml−1) or vehicle (saline) for one, two, three, or four injections every 90 min. These treatments were equivalent to 1.5, 3.0, 4.5, or 6 h of ketamine treatment. (a) Immunoblots from P7 brain lysates demonstrate that (b) ketamine increases cleaved caspase-3 and 9 expression after 4 h. (c) This mirrored decreases in phosphorylation of AKT and GSK-3β (n=6, **P<0.01 compared with control). Data are presented as mean (sem). British Journal of Anaesthesia  , i3-i9DOI: ( /bja/aet057) Copyright © 2013 The Author(s) Terms and Conditions

3 Fig 2 Ketamine-induced apoptosis detected by cleaved capsase-3 was attenuated by lithium. Immunohistochemistry with antibody to cleaved caspase-3 cortical sections from P7 rat pups (a) control, (b) lithium (Li), (c) lithium and ketamine (Li+KET), and (d) ketamine (KET) (scale bar=20 µm). (e) Quantitation of cleaved caspase-3-positive cells. (**P<0.01 compared with control.) Values are mean (sem, n=4). British Journal of Anaesthesia  , i3-i9DOI: ( /bja/aet057) Copyright © 2013 The Author(s) Terms and Conditions

4 Fig 3 Ketamine-induced apoptosis detected by TUNEL staining was attenuated by lithium. TUNEL staining of cortical sections from P7 rat pups: (a) control, (b) Li, (c) Li+KET, and (d) KET (scale bar=20 µm). (e) Quantitation of TUNEL-positive cells. (**P<0.01.) Values are mean (sem, n=4). British Journal of Anaesthesia  , i3-i9DOI: ( /bja/aet057) Copyright © 2013 The Author(s) Terms and Conditions

5 Fig 4 Lithium attenuated ketamine-induced cleaved caspase-3 and -9 expression. Cleaved caspase-3 and -9 protein was examined by (a) immunoblotting. (b) Lithium significantly decreased cleaved caspase-3, and -9 in comparison with the ketamine alone group. (**P<0.01.) Values are mean (sem, n=4). British Journal of Anaesthesia  , i3-i9DOI: ( /bja/aet057) Copyright © 2013 The Author(s) Terms and Conditions

6 Fig 5 Lithium attenuated ketamine-induced decreases in phosphorylation of AKT and GSK-3β Immunoblots (a) from P7 brain lysates demonstrates that (b) ketamine decreased phosphorylation of AKT and GSK-3β. Concurrent administration of lithium and ketamine attenuated this response. Lithium alone increased phosphorylation of AKT and GSK-3β. Values are mean (sem, n=4), *P<0.05, **P<0.01. British Journal of Anaesthesia  , i3-i9DOI: ( /bja/aet057) Copyright © 2013 The Author(s) Terms and Conditions

7 Fig 6 Lithium attenuated ketamine-induced increase in cyclin D1 expression. Immunoblot (a) from P7 brain lysates demonstrates that (b) lithium attenuated ketamine-induced expression of cyclin D1 (n=4, *P<0.05, **P<0.01). Data are presented as mean (sem). British Journal of Anaesthesia  , i3-i9DOI: ( /bja/aet057) Copyright © 2013 The Author(s) Terms and Conditions


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