PMID- 28425952 OWN - NLM STAT- MEDLINE DCOM- 20171026 LR - 20220311 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 4 DP - 2017 Apr 20 TI - Antioxidant and Anti-Senescence Effect of Metformin on Mouse Olfactory Ensheathing Cells (mOECs) May Be Associated with Increased Brain-Derived Neurotrophic Factor Levels-An Ex Vivo Study. LID - 10.3390/ijms18040872 [doi] LID - 872 AB - Metformin, the popular anti-diabetic drug was shown to exert multiple biological effects. The most recent metformin gained attention as an agent that mobilizes endogenous progenitor cells and enhances regenerative potential of organisms, for example by promoting neurogenesis. In the present study, we examined the role of metformin on mouse olfactory ensheathing cells (mOECs) derived from animals receiving metformin for eight weeks at a concentration equal to 2.8 mg/day. The mOECs expanded ex vivo were characterized in terms of their cellular phenotype, morphology, proliferative activity, viability and accumulation of oxidative stress factors. Moreover, we determined the mRNA and protein levels of brain-derived neurotrophic factor (BDNF), distinguishing the secretion of BDNF by mOECs in cultures and circulating serum levels of BDNF. The mOECs used in the experiment were glial fibrillary acidic protein (GFAP) and p75 neurotrophin receptor (p75(NTR)) positive and exhibited both astrocyte-like and non-myelin Schwann cell-like morphologies. Our results revealed that the proliferation of OECs derived from mice treated with metformin was lowered, when compared to control group. Simultaneously, we noted increased cell viability, reduced expression of markers associated with cellular senescence and a decreased amount of reactive oxygen species. We observed increased mRNA expression of BDNF and its down-stream genes. Obtained results indicate that metformin may exert antioxidant, anti-apoptotic and senolytic action on OECs expanded ex vivo. FAU - Smieszek, Agnieszka AU - Smieszek A AD - Department of Experimental Biology and Electron Microscope Facility, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland. agnieszka.smieszek@upwr.edu.pl. FAU - Strek, Zuzanna AU - Strek Z AD - Department of Experimental Biology and Electron Microscope Facility, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland. zuzanna.strek@gmail.com. FAU - Kornicka, Katarzyna AU - Kornicka K AD - Department of Experimental Biology and Electron Microscope Facility, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland. kornicka.katarzyna@gmail.com. FAU - Grzesiak, Jakub AU - Grzesiak J AD - Wroclaw Research Centre EIT+, Stablowicka 147, 54-066 Wroclaw, Poland. grzesiak.kuba@gmail.com. FAU - Weiss, Christine AU - Weiss C AD - PferdePraxis Dr. Med. Vet. Daniel Weiss, Postmatte 14, CH-8807 Freienbach, Switzerland. d.weiss@horsedoc.ch. FAU - Marycz, Krzysztof AU - Marycz K AD - Wroclaw Research Centre EIT+, Stablowicka 147, 54-066 Wroclaw, Poland. krzysztof.marycz@up.wroc.pl. LA - eng PT - Journal Article DEP - 20170420 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antioxidants) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 9100L32L2N (Metformin) SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Biomarkers MH - Brain-Derived Neurotrophic Factor/blood/*metabolism MH - Cell Survival/drug effects MH - Cells, Cultured MH - Female MH - Gene Expression Regulation/drug effects MH - Metformin/*pharmacology MH - Mice MH - Mitochondria/drug effects/metabolism MH - Neuroglia/cytology/*drug effects/*metabolism MH - Olfactory Bulb/*cytology MH - Oxidative Stress/drug effects/genetics MH - Phenotype MH - Signal Transduction/drug effects PMC - PMC5412453 OTO - NOTNLM OT - anti-oxidative OT - brain-derived neurotrophic factor OT - metformin OT - olfactory ensheathing cells OT - senolytic COIS- The authors declare no conflict of interest. EDAT- 2017/04/21 06:00 MHDA- 2017/10/27 06:00 PMCR- 2017/04/01 CRDT- 2017/04/21 06:00 PHST- 2017/03/15 00:00 [received] PHST- 2017/04/11 00:00 [revised] PHST- 2017/04/13 00:00 [accepted] PHST- 2017/04/21 06:00 [entrez] PHST- 2017/04/21 06:00 [pubmed] PHST- 2017/10/27 06:00 [medline] PHST- 2017/04/01 00:00 [pmc-release] AID - ijms18040872 [pii] AID - ijms-18-00872 [pii] AID - 10.3390/ijms18040872 [doi] PST - epublish SO - Int J Mol Sci. 2017 Apr 20;18(4):872. doi: 10.3390/ijms18040872.