PMID- 29512848 OWN - NLM STAT- MEDLINE DCOM- 20181023 LR - 20181023 IS - 1472-8206 (Electronic) IS - 0767-3981 (Linking) VI - 32 IP - 4 DP - 2018 Aug TI - Metformin ameliorates the age-related changes of d-galactose administration in ovariectomized mice. PG - 392-399 LID - 10.1111/fcp.12364 [doi] AB - Metformin (Met) has been shown to have pleiotropic effects such as neuroprotective, antioxidant, and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. This study was designed to investigate the possible effect of Met on the d-galactose (d-gal)-induced aging in ovariectomized mice. The female mice underwent bilateral ovariectomy. d-gal was administered orally at a dose of 500 mg/kg, and Met was administrated orally at doses of 1 and 10 mg/kg for 6 weeks. Anxiety-like behavior was evaluated by the elevated plus-maze. Physical power was assessed by vertical grid holding test and forced swimming capacity test. The brains were assessed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Ovariectomy caused anxiety and declined the physical power as well as BDNF and SOD levels. d-gal administration in ovariectomized mice exacerbated these deleterious effects. Met hampered the anxiety-like behavior and strengthened the physical power of d-gal-treated ovariectomized mice. Met also increased the SOD and BDNF levels in the brains of d-gal-treated ovariectomized animals. Based on the obtained results, we suggest Met administration as a novel therapeutic approach for the treatment of age-related conditions in the absence of female sex hormones. CI - (c) 2018 Societe Francaise de Pharmacologie et de Therapeutique. FAU - Fatemi, Iman AU - Fatemi I AUID- ORCID: 0000-0002-9666-9651 AD - Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. AD - Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. FAU - Heydari, Sara AU - Heydari S AD - Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. FAU - Kaeidi, Ayat AU - Kaeidi A AD - Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. AD - Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. FAU - Shamsizadeh, Ali AU - Shamsizadeh A AD - Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. AD - Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. FAU - Hakimizadeh, Elham AU - Hakimizadeh E AD - Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. AD - Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. FAU - Khaluoi, Amin AU - Khaluoi A AD - Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. FAU - Allahtavakoli, Mohammad AU - Allahtavakoli M AD - Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. AD - Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7717684884, Iran. LA - eng PT - Journal Article DEP - 20180423 PL - England TA - Fundam Clin Pharmacol JT - Fundamental & clinical pharmacology JID - 8710411 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 9100L32L2N (Metformin) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - X2RN3Q8DNE (Galactose) SB - IM MH - Aging/*drug effects/metabolism MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Antioxidants/pharmacology MH - Brain/drug effects/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Female MH - Galactose/*pharmacology MH - Maze Learning/drug effects MH - Metformin/*pharmacology MH - Mice MH - Neuroprotective Agents/pharmacology MH - Ovariectomy/methods MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - aging OT - d-galactose OT - metformin OT - ovariectomy EDAT- 2018/03/08 06:00 MHDA- 2018/10/24 06:00 CRDT- 2018/03/08 06:00 PHST- 2017/12/04 00:00 [received] PHST- 2018/02/17 00:00 [revised] PHST- 2018/02/28 00:00 [accepted] PHST- 2018/03/08 06:00 [pubmed] PHST- 2018/10/24 06:00 [medline] PHST- 2018/03/08 06:00 [entrez] AID - 10.1111/fcp.12364 [doi] PST - ppublish SO - Fundam Clin Pharmacol. 2018 Aug;32(4):392-399. doi: 10.1111/fcp.12364. Epub 2018 Apr 23.