Linking Redox Regulation of NMDAR Synaptic Function to Cognitive Decline during Aging
Ashok Kumar and Thomas C. Foster J.
Neurosci. 2013;33 15710-15715
In middle-age, many people will begin to experience impairments in the ability to remember spatial information that is normally acquired rapidly and automatically. Where did I put my keys, glasses, etc.? Our research provides new insights into this annoying problem. Cell metabolism results in oxidative stress due to the release of superoxide, a molecule that causes irreversible damage to cells. In neurodegenerative diseases such as Alzheimer’s disease or Parkinson’s disease, damaged molecules may accumulate causing severe problems for brain function. Normally, the highly toxic superoxide is controlled by antioxidant enzymes in the cells that convert superoxide to hydrogen peroxide and water. In turn, hydrogen peroxide can change the shape and function of proteins, called redox state, to act as a reversible signal of superoxide levels.
Our research indicates redox state changes also occur in the function of proteins involved in learning and memory. Specifically, the redox state of these proteins affects synaptic plasticity, the process of rapidly increasing the communication between cells at synaptic contacts as we learn about our environment. This early step in the memory process is used to quickly store information that can be used over the next several minutes or hours.
In the current paper we show that, like humans, middle-age rodents begin to exhibit learning and memory deficits for rapidly acquired spatial information. Furthermore, those animals with impaired memory exhibit impaired synaptic plasticity and these modifications are due to reversible redox state changes in cells. The results provide a link between processes of biological aging such as increased oxidative stress and those annoying cognitive changes that emerge in middle-age. The results also suggest how adjustments in our lifestyle can influence oxidative stress and memory. What we don’t know is whether these early changes, observed in some animals, will lead to more severe memory problems with advancing age.