Abstract
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 (p75NTR) 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.
Highlights
Metformin (MET) is considered a first-line pharmacological treatment for type 2 diabetes (T2D)
Our analysis showed that the formation of lamellipodia was more visible in cultures of mouse olfactory ensheathing cells (mOECs) derived from MET animals
Our results suggest that metformin may modulate antigen plasticity of mOECs, as evidenced by increased expression of p75 neurotrophin receptor (p75NTR) and decreased expression of glial fibrillary acidic protein (GFAP) (Figure 2)
Summary
Metformin (MET) is considered a first-line pharmacological treatment for type 2 diabetes (T2D). Metformin gained attention as an effective next-generation drug, which can find application in regenerative medicine for the treatment of age-related diseases [6]. Neuroprotective effects of metformin have been confirmed by a recent study of Chen et al [13] who investigated the effects of anti-diabetic drugs on hippocampal synaptic plasticity using mice models. These authors showed that metformin could exert anti-apoptotic effects by decreasing the ratio of caspase-3 fragment/procaspase-3 and increasing the ratio of Bcl-2/Bax in the hippocampus. Metformin can enhance olfactory neurogenesis, resulting in a significantly increased number of BrdU-positive and NeuN-positive olfactory neurons in the granule cell layer [7]
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