Metformin administration prevents memory impairment induced by hypobaric hypoxia in rats

Metformin, an antidiabetic biguanide, reduces hyperglycemia by improving glucose utilization and reducing gluconeogenesis. Recently, an increasing number of studies have shown that metformin also led to a significant clinical improvement in memory and cognition in different clinical settings. In the present study, we investigated whether metformin administration protects against memory impairment and neuron damage caused by acute exposure to hypobaric hypoxia and screened the possible molecular mechanisms with a focused gene array. We found that metformin treatment obviously attenuated spatial memory and recognition memory impairment resulting from acute hypobaric hypoxia exposure but had no effect on general locomotor and behavioral activity. Moreover, the results of Nissl and TUNEL staining showed that neuron damage and cell apoptosis caused by hypobaric hypoxia exposure was also inhibited by metformin pretreatment. At the molecular level, we found that metformin pretreatment not only prevented the changes of FOS, JUNB and BDNF at both mRNA and protein levels, but also increased the expression of the postsynaptic scaffold genes HOMER and PSD95 after exposure to hypobaric hypoxia. These data suggested that metformin pretreatment is a feasible strategy for preventing memory impairment under hypobaric hypoxia.