Metformin ameliorates the age‐related changes of d‐galactose administration in ovariectomized mice

Abstract

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.

Pro‐neurocognitive and anti‐sarcopenic benefits of one‐year metformin therapy in ovariectomized aged mice

“…Three days after ovariectomy vaginal smears were taken and observed under the light microscope for 6 days. The ovariectomy was confirmed if cornified epithelial cells were not observed in the vaginal smear . The mice in the sham group underwent the same surgical procedure without removal of the ovaries.…”

“…Elevated plus maze (EPM) is a standard method to evaluate anxiety‐like behavior in rodents . EPM apparatus consisted of four arms arranged in the shape of a plus sign (two closed and two open arms with similar size [50 × 10 cm]) and were connected to a central square platform (10 × 10 cm).…”

“…The mouse was returned five times to the grid after falling. The time before the fifth fall was reported as the physical power of the animal …”

“…Exhaustion was determined by observing loss of coordinated movements and failure to return to the surface within 7 seconds, and the time was recorded immediately. Afterwards, they were removed from water, dried via a paper towel and returned to the cages …”

“…Reports have shown that Met acts as an anti‐aging agent and is associated with a reduction in the incidence of cancer and mortality . It has been reported that Met treatment increases BDNF levels, neurogenesis, improves memory, learning processes and reduces cognitive decline risk or dementia …”