Metformin May Find New Role in the Treatment of Brain Disorders

Metformin is a widely used medication that is the drug of choice to treat type 2 diabetics who are overweight or obese because it does not cause weight gain.  Metformin has been shown to be very safe and to reduce diabetes associated complications such as heart disease and stroke.  Metformin is contraindicated in any patient that has an increased risk of lactic acidosis, such as patients that have renal insufficiency.  In addition, metformin should be discontinued or held in patients who are scheduled to receive iodinated contrast dye for CT scans or angiograms because the contrast can impair kidney function and predispose to lactic acidosis.  Metformin works by decreasing glucose production in the liver (hepatic gluconeogenesis).  Metformin activates AMP-activated protein kinase (AMPK) in the liver.  AMPK goes on to inhibit the express of genes that are involved in hepatic gluconeogenesis.

Researchers, lead by Dr. Freda Miller from the Hospital for Sick Children in Toronto, have shown that metformin can promote the growth and development of nerve cells in the brain and could potentially be useful in the treatment of brain disorders.  The results of their work were published online in the journal Cell Stem Cell.  The researchers have found that metformin activates the atypical PKC-CBP signaling pathway in neuronal stem cells that causes nerve cell differentiation and development.  Cultured mouse neuronal precursors that are exposed to metformin are induced to differentiate into nerve cells.  This was also found to be true for cultured human neuronal precursor cells.  In addition, mice treated with metformin were shown to have increased neuronal development in an area of the brain called the hippocampus, which is involved in learning and memory formation.  In addition, the researchers were able to show that metformin treated mice were able to learn maze layouts faster and retain the maze memory for longer that untreated mice.

The authors wrote, “there is widespread interest in using metformin in individuals with early-stage Alzheimer’s disease because an increasing proportion of these individuals are also diabetic, and hyperinsulinemia may enhance the onset and progression of neurodegeneration… metformin has been shown to increase lifespan and delay the onset of cognitive impairment in a mouse model of Huntington’s disease.  Thus, while metformin may have other actions in the nervous system, our findings raise the possibility that its ability to enhance neurogenesis might have a positive impact in at least some nervous system disorders”.

The use of stem cells to treat neuro-degenerative disorder such as Alzheimer’s dementia and Huntington’s chorea is still in the early experimental stages.  This research suggests that using exogenous medications may be a viable method to stimulate the brain’s own stem cells to differentiate into nerve cells and cause repair of brain injuries.  Futures studies should focus on identifying other medications that can be used to induce differentiation and development of nerve cells within the brain.  In addition, future studies will need to show that metformin can improve memory in humans with a predisposition for memory deficits, such as in Alzheimer’s dementia.

See the following YouTube video with Dr. Freda Miller about the research findings:

Reference:

Jing Wang et al. “Metformin Activates an Atypical PKC-CBP Pathway to Promote Neurogenesis and Enhance Spatial Memory Formation” Cell Stem Cell – 6 July 2012 (Vol. 11, Issue 1, pp. 23-35)

Tagged as: Alzheimer’s dementia, Alzheimer’s disease, atypical PKC-CBP signaling pathway, diabetes, Dr. Freda Miller, heart disease, hepatic gluconeogenesis, hippocampus, Huntington’s chorea, lactic acidosis, metformin, renal insufficiency, stem cells, stroke, type 2 diabetes