Neuroscientists pinpoint the key to keeping your mind sharp into old age

Separate from some more serious problems like dementia and Alzheimer’s disease, memory-making and cognitive abilities weaken somewhat as we age. But according to new studies, this biological mental decline can be halted and possibly remedied.

Kathy Magnusson, a neuroscientist in the OSU Department of Biomedical Sciences, College of Veterinary Medicine, and professor in the Linus Pauling Institute is conducting research on how to prevent or repair the declines that occur during aging in learning and memory ability.

She says, as an aging neuroscientist herself: “I’m hoping to figure this out before I forget what the question is.”

The researchers have pinpointed a receptor that is very important for the formation of memories, the N-methyl-D-aspartate (NMDA) receptor. This receptor uses glutamate as a transmitter. The NMDA receptor shows greater declines in binding of glutamate with increased age than any of the other glutamate receptors. They also are targeting two NMDA receptor subunits, GluN2B and GluN2A during aging.

The NMDA receptor has been known of for decades, Magnusson said. It plays a role in memory and learning but isn’t active all the time ? it takes a fairly strong stimulus of some type to turn it on and allow you to remember something. The routine of getting dressed in the morning is ignored and quickly lost to the fog of time, but the day you had an auto accident earns a permanent etching in your memory.

In recent research, supported by the National Institutes of Health, OSU scientists used a genetic therapy in laboratory mice, in which a virus helped carry complementary DNA into appropriate cells and restored some GluN2B subunits. Tests showed that it helped mice improve their memory and cognitive ability.

According to this study and others, many different interventions have been used successfully in vivo to attenuate the effect of aging on the NMDA receptor complex:

• Acetyl-L-carnitine (ALCAR), a compound that demonstrates multiple anti-aging effects in the brain when administered systemically to an aged, improves antagonist binding to the NMDA binding site.
• Other cognitive enhancing and free radical scavenging drugs such as vitamin E and alpha-lipoic acid.
• Caloric restriction is an aging intervention that has been shown to improve memory performance especially in spatial tasks.
• Other dietary interventions, such as dietary supplementation with omega-3 polyunsaturated fatty acids , decreasing oxidative stress and declines in the brain.
• Dietary supplementation with blueberry extract in aged rats rescues NMDA receptor-dependent LTP in the hippocampus, but did not prevent aged related declines in the protein expression of the GluN1 or GluN2B subunits.
• Drug related interventions have shown promise for reversing age-related cognitive deficits. Nicotine reversed the effects of aging on the GluN2B subunit in the hippocampus, but showed no influence on expression of the GluN2A subunit.

Within the NMDA receptor are various subunits, and Magnusson said that research keeps pointing back to the GluN2B subunit as one of the most important. Infants and children have lots of them, and as a result are like a sponge in soaking up memories and learning new things. But they gradually dwindle in number with age, and it also appears the ones that are left work less efficiently.

“You can still learn new things and make new memories when you are older, but it’s not as easy,? Magnusson said. “Fewer messages get through, fewer connections get made, and your brain has to work harder.?

Until more specific help is available, she said, some of the best advice for maintaining cognitive function is to keep using your brain. Break old habits, do things different ways. Get physical exercise, maintain a good diet and ensure social interaction. Such activities help keep these “subunits? active and functioning.

Resources:

Cognitive decline with age is normal, routine ? but not inevitable Oregon State University

Selective vulnerabilities of N-methyl-D-aspartate (NMDA) receptors during brain aging Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA