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Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice.
Can J Physiol Pharmacol. 2017 Dec; 95(12):1396-1405.CJ

Abstract

Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7. EGCG significantly inhibited sevoflurane-induced neuroapoptosis as determined by Fluoro-Jade B staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Increased levels of cleaved caspase-3, downregulated Bad and Bax, and significantly enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, and survivin expression were observed. EGCG induced activation of the PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3β, phospho-GSK-3β, and mTORc1 levels. Sevoflurane-mediated downregulation of cAMP/CREB and BDNF/TrkB signalling was inhibited by EGCG. Reverse transcription PCR analysis revealed enhanced BDNF and TrkB mRNA levels upon EGCG administration. Improved performance of mice in Morris water maze tests suggested enhanced learning and memory. The study indicates that EGCG was able to effectively inhibit sevoflurane-induced neurodegeneration and improve learning and memory retention of mice via activation of CREB/BDNF/TrkB-PI3K/Akt signalling.

Authors+Show Affiliations

a Department of Pediatrics, Shandong Jining No. 1 People's Hospital, Shandong 272011, China.b Department of Neurosurgery, Shandong Jining No. 1 People's Hospital, Shandong 272011, China.a Department of Pediatrics, Shandong Jining No. 1 People's Hospital, Shandong 272011, China.a Department of Pediatrics, Shandong Jining No. 1 People's Hospital, Shandong 272011, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28679060

Citation

Ding, Mei-Li, et al. "Protective Effects of a Green Tea Polyphenol, Epigallocatechin-3-gallate, Against Sevoflurane-induced Neuronal Apoptosis Involve Regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR Signalling Pathways in Neonatal Mice." Canadian Journal of Physiology and Pharmacology, vol. 95, no. 12, 2017, pp. 1396-1405.
Ding ML, Ma H, Man YG, et al. Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice. Can J Physiol Pharmacol. 2017;95(12):1396-1405.
Ding, M. L., Ma, H., Man, Y. G., & Lv, H. Y. (2017). Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice. Canadian Journal of Physiology and Pharmacology, 95(12), 1396-1405. https://doi.org/10.1139/cjpp-2016-0333
Ding ML, et al. Protective Effects of a Green Tea Polyphenol, Epigallocatechin-3-gallate, Against Sevoflurane-induced Neuronal Apoptosis Involve Regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR Signalling Pathways in Neonatal Mice. Can J Physiol Pharmacol. 2017;95(12):1396-1405. PubMed PMID: 28679060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice. AU - Ding,Mei-Li, AU - Ma,Hui, AU - Man,Yi-Gang, AU - Lv,Hong-Yan, Y1 - 2017/07/05/ PY - 2017/7/6/pubmed PY - 2018/6/15/medline PY - 2017/7/6/entrez KW - brain-derived neurotrophic factor KW - cAMP response element-binding protein KW - epigallocatechin-3-gallate KW - facteur neurotrophique dérivé du cerveau KW - neurodegeneration KW - neurodégénérescence KW - phosphatidylinositol 3-kinase signalling KW - protéine de liaison d’éléments-AMPc répondante KW - sevoflurane KW - voie de signalisation de la phosphatidylinositol 3-kinase KW - épigallocatéchine-3-gallate SP - 1396 EP - 1405 JF - Canadian journal of physiology and pharmacology JO - Can. J. Physiol. Pharmacol. VL - 95 IS - 12 N2 - Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7. EGCG significantly inhibited sevoflurane-induced neuroapoptosis as determined by Fluoro-Jade B staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Increased levels of cleaved caspase-3, downregulated Bad and Bax, and significantly enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, and survivin expression were observed. EGCG induced activation of the PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3β, phospho-GSK-3β, and mTORc1 levels. Sevoflurane-mediated downregulation of cAMP/CREB and BDNF/TrkB signalling was inhibited by EGCG. Reverse transcription PCR analysis revealed enhanced BDNF and TrkB mRNA levels upon EGCG administration. Improved performance of mice in Morris water maze tests suggested enhanced learning and memory. The study indicates that EGCG was able to effectively inhibit sevoflurane-induced neurodegeneration and improve learning and memory retention of mice via activation of CREB/BDNF/TrkB-PI3K/Akt signalling. SN - 1205-7541 UR - https://www.unboundmedicine.com/medline/citation/28679060/Protective_effects_of_a_green_tea_polyphenol_epigallocatechin_3_gallate_against_sevoflurane_induced_neuronal_apoptosis_involve_regulation_of_CREB/BDNF/TrkB_and_PI3K/Akt/mTOR_signalling_pathways_in_neonatal_mice_ L2 - http://www.nrcresearchpress.com/doi/full/10.1139/cjpp-2016-0333?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -