Common Diabetes Drug Found to Stimulate Brain Cell Growth, May Treat Alzheimer's and Stroke Patients

Shown here is a hippocampal neuron transfected with Yellow-Fluorescent Protein (YFP) tagged transglutaminase under control conditions.
In MS, the protective sheath of neurons is attacked by the immune system. A new modification of a currently used treatment will allow for longer time between doses with the same results. NIH

A commonly used diabetes drug metformin may also be used to treat nervous system damage, according to new findings that suggest that the drug encourages the growth of brain cells.

A new study published in the journal Cell Stem Cell, showed in a series of experiments that the drug which promoted the growth of new neurons appeared to make mice smarter.

Co-researcher Dr. Freda Miller of the Hospital for Sick Children in Toronto, and colleagues performed a classic behavioral test on mice and found that mice treated with metformin formed new memories significantly quicker that those given a control substance.

Miller and colleagues had previously found that a molecule called CREB-binding protein, or CBP, was needed to maximize the development of embryonic neural precursor cells and that the protein needed to be activated by another molecule called atypical protein kinase C, or aPKC.

They had predicted that metformin might activate the aPKC-CBP pathway in neural stem cells leading to the creation of new neurons, and in the recent series of experiments, they were able to prove that metformin does indeed promotes neurogenesis, both in mouse and human neural stem cells.

Researchers found that metformin nearly doubled the number of new neurons that were produced by stem cells compared to controls in one experiment.

In living mice researchers found that 12 days on metformin increased the number of new neurons in the hippocampus or the area of the brain involved in making new memories, by about 30 percent compared to controls.

Furthermore, they found that mice that were injected with 200 milligrams per kilogram of brain boosting metformin were significantly more able to learn and memorize the location of a hidden platform in a standard spatial learning maze test compared to those given saline for 38 days.

Researchers noted using stem cells to generate new neurons is an attractive therapy, but treatments using either growth factors or small molecules have so far not panned out, and suggest that metformin, which is widely used as a treatment for type II diabetes and other metabolic disorders, be considered as a treatment to improve Alzheimer's symptoms by enhancing brain repair.

Miller and colleagues suggested that metformin or something like it might be a "candidate pharmacological approach for nervous system therapy" in conditions such as ischemic stroke, Alzheimer's disease and other conditions where patients possess an injured or degenerating brain.

Intriguingly, 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," researchers added. "In this regard, a recent retrospective study indirectly suggested that metformin might improve some of the adverse neuroanatomical outcomes associated with Alzheimer'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," they concluded.

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