Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea is an effective antioxidant and possesses neuroprotective effects. For neurogenesis and synaptic plasticity, brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucially involved. In this study we aimed to assess 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 b.wt) 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 FluroJade B staining and TUNEL assay. Increased levels of cleaved caspase-3, down-regulated Bad and Bax with significantly enhanced Bcl-2, Bcl-xL, xIAP,c-IAP-1 and survivin expression were observed. EGCG induced activation of PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3β, phospho- GSK-3β and mTORc1 levels. Sevoflurane-mediated down-regulation of cAMP/CREB and BDNF-TrkB signalling were inhibited by EGCG. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels on EGCG administration. Improved performance of mice in Morris water maze tests suggests 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.

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