PMID- 29951932 OWN - NLM STAT- MEDLINE DCOM- 20181025 LR - 20181114 IS - 1573-6830 (Electronic) IS - 0272-4340 (Linking) VI - 38 IP - 6 DP - 2018 Aug TI - Minocycline Promotes BDNF Expression of N2a Cells via Inhibition of miR-155-Mediated Repression After Oxygen-Glucose Deprivation and Reoxygenation. PG - 1305-1313 LID - 10.1007/s10571-018-0599-0 [doi] AB - Minocycline, an anti-infective agent of a tetracycline derivative, is reported to improve behavioral functional recovery after cerebral ischemia via enhancing the levels of brain-derived neurotrophic factor (BDNF). However, the precise mechanisms that minocycline targets to enhance the expression of BDNF are not fully defined. In the present study, we observed the neuroprotective effect and its potential mechanisms of minocycline using oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N2a cells. We found that 50 microM minocycline protected against neuronal apoptosis induced by OGD/R injury, with increased expression ratio of Bcl-2/Bax and reduced expression of caspase-3. Interestingly, minocycline resulted in the up-regulation of only BDNF protein, not BDNF mRNA in N2a cells treated with OGD/R. Furthermore, we found that minocycline inhibited OGD/R-induced up-regulation of miR-155 targeted BDNF transcripts. Moreover, miR-155 mimic could partially abolish the neuroprotective effects of minocycline via inhibiting the levels of BDNF protein. These findings suggest that minocycline is neuroprotective against ischemic brain injury through their modulation of miR-155-mediated BDNF repression. FAU - Lu, Yunnan AU - Lu Y AD - Department of Neurology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, 214000, Jiangsu, China. FAU - Huang, Zhichao AU - Huang Z AD - Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Rd, Gusu District, Suzhou, 215004, Jiangsu, China. FAU - Hua, Ye AU - Hua Y AD - Department of Neurology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, 214000, Jiangsu, China. FAU - Xiao, Guodong AU - Xiao G AD - Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Rd, Gusu District, Suzhou, 215004, Jiangsu, China. Parsley_shaw@hotmail.com. LA - eng PT - Journal Article DEP - 20180627 PL - United States TA - Cell Mol Neurobiol JT - Cellular and molecular neurobiology JID - 8200709 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 0 (Neuroprotective Agents) RN - FYY3R43WGO (Minocycline) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Brain/drug effects/metabolism MH - Brain Ischemia/*genetics/metabolism MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Glucose/*metabolism MH - Mice MH - MicroRNAs/*genetics MH - Minocycline/*pharmacology MH - Neurons/metabolism MH - Neuroprotective Agents/metabolism MH - Oxygen/*metabolism MH - Signal Transduction/drug effects OTO - NOTNLM OT - BDNF OT - Ischemia stroke OT - MiR-155 OT - Minocycline OT - Oxygen-glucose deprivation and reoxygenation EDAT- 2018/06/29 06:00 MHDA- 2018/10/26 06:00 CRDT- 2018/06/29 06:00 PHST- 2018/04/26 00:00 [received] PHST- 2018/06/21 00:00 [accepted] PHST- 2018/06/29 06:00 [pubmed] PHST- 2018/10/26 06:00 [medline] PHST- 2018/06/29 06:00 [entrez] AID - 10.1007/s10571-018-0599-0 [pii] AID - 10.1007/s10571-018-0599-0 [doi] PST - ppublish SO - Cell Mol Neurobiol. 2018 Aug;38(6):1305-1313. doi: 10.1007/s10571-018-0599-0. Epub 2018 Jun 27.