PMID- 29427085 OWN - NLM STAT- MEDLINE DCOM- 20190204 LR - 20210109 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 55 IP - 9 DP - 2018 Sep TI - Regulatory Effects of Neuroinflammatory Responses Through Brain-Derived Neurotrophic Factor Signaling in Microglial Cells. PG - 7487-7499 LID - 10.1007/s12035-018-0933-z [doi] AB - Inhibition of microglial over-activation is an important strategy to counter balance neurodegenerative progression. We previously demonstrated that the adenosine monophosphate-activated protein kinase (AMPK) may be a therapeutic target in mediating anti-neuroinflammatory responses in microglia. Brain-derived neurotrophic factor (BDNF) is one of the major neurotrophic factors produced by astrocytes to maintain the development and survival of neurons in the brain, and have recently been shown to modulate homeostasis of neuroinflammation. Therefore, the present study focused on BDNF-mediated neuroinflammatory responses and may provide an endogenous regulation of neuroinflammation. Among the tested neuroinflammation, epigallocatechin gallate (EGCG) and minocycline exerted BDNF upregulation to inhibit COX-2 and proinflammatory mediator expressions. Furthermore, both EGCG and minocycline upregulated BDNF expression in microglia through AMPK signaling. In addition, minocycline and EGCG also increased expressions of erythropoietin (EPO) and sonic hedgehog (Shh). In the endogenous modulation of neuroinflammation, astrocyte-conditioned medium (AgCM) also decreased the expression of COX-2 and upregulated BDNF expression in microglia. The anti-inflammatory effects of BDNF were mediated through EPO/Shh in microglia. Our results indicated that the BDNF-EPO-Shh novel-signaling pathway underlies the regulation of inflammatory responses and may be regarded as a potential therapeutic target in neurodegenerative diseases. This study also reveals a better understanding of an endogenous crosstalk between astrocytes and microglia to regulate anti-inflammatory actions, which could provide a novel strategy for the treatment of neuroinflammation and neurodegenerative diseases. FAU - Lai, Sheng-Wei AU - Lai SW AD - Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. FAU - Chen, Jia-Hong AU - Chen JH AD - Department of General Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan. AD - School of Medicine, Tzu Chi University, Hualien, Taiwan. FAU - Lin, Hsiao-Yun AU - Lin HY AD - Department of Pharmacology, School of Medicine, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan. FAU - Liu, Yu-Shu AU - Liu YS AD - Department of Pharmacology, School of Medicine, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan. AD - Department of Biotechnology, Asia University, Taichung, Taiwan. FAU - Tsai, Cheng-Fang AU - Tsai CF AD - Department of Biotechnology, Asia University, Taichung, Taiwan. FAU - Chang, Pei-Chun AU - Chang PC AD - Department of Bioinformatics, Asia University, Taichung, Taiwan. FAU - Lu, Dah-Yuu AU - Lu DY AUID- ORCID: 0000-0002-4463-5919 AD - Department of Pharmacology, School of Medicine, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan. dahyuu@mail.cmu.edu.tw. AD - Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan. dahyuu@mail.cmu.edu.tw. FAU - Lin, Chingju AU - Lin C AD - Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan. clin33@mail.cmu.edu.tw. LA - eng GR - 102-2320-B-039 -026 -MY3/Ministry of Science and Technology, Taiwan (TW)/ GR - CMU105-AWARD-01/China Medical University/ GR - TTCRD104-13/Taichung Tzu Chi Hospital/ GR - MOHW106-TDU-B-212-113004/Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence/ PT - Journal Article DEP - 20180209 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 0 (Hedgehog Proteins) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (Neuroprotective Agents) RN - 11096-26-7 (Erythropoietin) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - FYY3R43WGO (Minocycline) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Astrocytes/drug effects/metabolism MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Catechin/analogs & derivatives/pharmacology MH - Cell Line MH - Culture Media, Conditioned/pharmacology MH - Cyclooxygenase 2/metabolism MH - Erythropoietin/metabolism MH - Hedgehog Proteins/metabolism MH - Humans MH - Inflammation/*pathology MH - Inflammation Mediators/metabolism MH - Lipopolysaccharides MH - Mice MH - Microglia/drug effects/*metabolism/pathology MH - Minocycline/pharmacology MH - Models, Biological MH - Neuroprotective Agents/pharmacology MH - *Signal Transduction OTO - NOTNLM OT - Astrocytes OT - BDNF OT - Cox-2 OT - Microglia OT - Neuroinflammation EDAT- 2018/02/11 06:00 MHDA- 2019/02/05 06:00 CRDT- 2018/02/11 06:00 PHST- 2017/07/18 00:00 [received] PHST- 2018/01/25 00:00 [accepted] PHST- 2018/02/11 06:00 [pubmed] PHST- 2019/02/05 06:00 [medline] PHST- 2018/02/11 06:00 [entrez] AID - 10.1007/s12035-018-0933-z [pii] AID - 10.1007/s12035-018-0933-z [doi] PST - ppublish SO - Mol Neurobiol. 2018 Sep;55(9):7487-7499. doi: 10.1007/s12035-018-0933-z. Epub 2018 Feb 9.