PMID- 30189852 OWN - NLM STAT- MEDLINE DCOM- 20190819 LR - 20231213 IS - 1471-2202 (Electronic) IS - 1471-2202 (Linking) VI - 19 IP - 1 DP - 2018 Sep 6 TI - Involvement of Akt/CREB signaling pathways in the protective effect of EPA against interleukin-1beta-induced cytotoxicity and BDNF down-regulation in cultured rat hippocampal neurons. PG - 52 LID - 10.1186/s12868-018-0455-7 [doi] LID - 52 AB - BACKGROUND: Our published data have indicated that the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) provides beneficial effects by attenuating neuronal damage induced by interleukin-1beta (IL-1beta), and up-regulation of the expression of brain-derived neurotrophic factor (BDNF) represents a crucial part in the neuroprotective effect of EPA. However, the mechanisms of how EPA regulates BDNF expression remains incompletely understood. The present study investigated the role of Akt/CREB signaling in the effect of EPA on BDNF expression and its neuroprotective effect. RESULTS: The present results showed that IL-1beta reduced hippocampal neuronal viability and that EPA showed a concentration-dependent neuroprotective effect, but the neuroprotective effects of EPA were abolished by inhibition of Akt using KRX-0401, an inhibitor of Akt. Treatment of hippocampal neurons with EPA also ameliorated the decrease in Akt and CREB phosphorylation induced by IL-1beta and BDNF down-regulation mediated by IL-1beta. However, inhibition of Akt reversed the effect of EPA on levels of p-Akt, p-CREB, and BDNF. CONCLUSIONS: Our data indicate that EPA elicited neuroprotection toward IL-1beta-induced cell damage and BDNF decrease and that its effects potentially occurred via the Akt/CREB signaling pathway. FAU - Dong, YiLong AU - Dong Y AUID- ORCID: 0000-0002-6078-1924 AD - School of Medicine, Yunnan University, 2 Cuihu Bei Road, Kunming, 650091, Yunnan, People's Republic of China. dongyilongmail@126.com. FAU - Pu, KangJing AU - Pu K AD - School of Medicine, Yunnan University, 2 Cuihu Bei Road, Kunming, 650091, Yunnan, People's Republic of China. FAU - Duan, WenJing AU - Duan W AD - The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650031, Yunnan, People's Republic of China. FAU - Chen, HuiCheng AU - Chen H AD - School of Medicine, Yunnan University, 2 Cuihu Bei Road, Kunming, 650091, Yunnan, People's Republic of China. FAU - Chen, LiXing AU - Chen L AD - The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650031, Yunnan, People's Republic of China. FAU - Wang, YanMei AU - Wang Y AD - The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650031, Yunnan, People's Republic of China. yaner6922@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180906 PL - England TA - BMC Neurosci JT - BMC neuroscience JID - 100966986 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, rat) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Interleukin-1beta) RN - 0 (Neuroprotective Agents) RN - AAN7QOV9EA (Eicosapentaenoic Acid) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects MH - Eicosapentaenoic Acid/*pharmacology MH - Hippocampus/*drug effects/metabolism MH - Interleukin-1beta/*metabolism/toxicity MH - Neurons/drug effects/metabolism MH - Neuroprotective Agents/*pharmacology MH - Primary Cell Culture MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects PMC - PMC6128001 OTO - NOTNLM OT - *Akt OT - *Brain-derived neurotrophic factor OT - *Eicosapentaenoic acid OT - *Interleukin-1beta EDAT- 2018/09/08 06:00 MHDA- 2019/08/20 06:00 PMCR- 2018/09/06 CRDT- 2018/09/08 06:00 PHST- 2018/03/19 00:00 [received] PHST- 2018/08/31 00:00 [accepted] PHST- 2018/09/08 06:00 [entrez] PHST- 2018/09/08 06:00 [pubmed] PHST- 2019/08/20 06:00 [medline] PHST- 2018/09/06 00:00 [pmc-release] AID - 10.1186/s12868-018-0455-7 [pii] AID - 455 [pii] AID - 10.1186/s12868-018-0455-7 [doi] PST - epublish SO - BMC Neurosci. 2018 Sep 6;19(1):52. doi: 10.1186/s12868-018-0455-7.