New results show that the adverse effects of cadmium on learning and memory can be reversed by stimulating neurogenesis in the hippocampus.
To date, research into the development of Alzheimer's Disease has focused primarily on genetics. Less attention has been given to the role of environmental exposures. However, research from UW SRP Project 2, carried out in the lab of Zhengui Xia, suggested that exposures to contaminants are also relevant, and, surprisingly, that cadmium may play an important role.
Cadmium is a heavy metal with industrial applications that is known to cause diseases of the kidney, liver, and bone, as well as cancer. For average Americans, the most common route of exposure to cadmium is through smoking or food. Over the last couple decades, research has accumulated suggesting that cadmium may also play a role as a neurotoxicant, even at low levels similar to those seen in the average, non-smoking U.S. population.
Recently, researchers in Xia's lab have used a mouse model to demonstrate that exposure to relatively low levels of cadmium in adulthood impairs olfaction, learning and memory, and the formation of new neurons (neurogenesis) in the hippocampus, a part of the brain involved in learning and the formation of memory, and in the olfactory bulb, a part of the brain important for olfaction. These results have important implications for the role of environmental exposures in the development of Alzheimer's Disease.
Now two new papers by Dr. Hao Wang, a post-doctoral trainee in the lab of Zhengui Xia, show that some of these adverse effects can be counteracted by stimulating neurogenesis in the adult brain. These results provide important evidence that the olfactory and cognitive deficits found previously after exposure to cadmium are indeed caused, at least in part, by disruptions to the formation and maturation of new neurons in the brain.
In order to be able to stimulate neurogenesis, Wang and his colleagues bred specialized "knock-in" mice that when treated with tamoxifen, express a specific kind of an enzyme known as an active MEK5 specifically in the stem cells in the brain. This active MEK5 activates another kinase involved in neurogenesis in the brain. The result is that treating these "knock-in" mice with tamoxifen stimulates neurogenesis in the adult brain. This creates an effective tool for testing the mechanism by which cadmium impairs olfaction as well as memory formation.
Both the toxic effects of cadmium on olfactory and cognitive function and the restorative effects of tamoxifen lasted well beyond the period of experimental cadmium exposure, suggesting that cadmium's neurotoxic effects are long-lasting. This emphasizes the importance of limiting environmental exposures to cadmium in order to minimize its contributions to neurodegenerative diseases like Alzheimer's.
Complete reports for the two studies can be found here and here.