Mouse studies suggest cause, preventive action

In the first study, the researchers examined CaM kinase II (CaMKII), an enzyme involved in, among other things, processes, synaptic plasticity and the transmission of nerve impulses across synapses.

By altering this brain protein in mice, they mimicked the cognitive effects that occur during normal aging.

A previous study by the same authors suggested that nitric oxide (NO) affects the action of CaMKII. This study took that research further and found that a process called S-nitrosylationwhich is dependent on NO, modifies CaMKII.

If nitrosylation of CaMKII is reduced, which occurs during normal aging, memory and learning are impaired.

Study author Prof. Ulli Bayerfrom the University of Colorado Anschutz School of Medicine, explained to Medical News Today how this can happen.

“The reduced nitrosylation of CaMKII causes a reduction in synaptic localization of CaMKII, which appeared to impair its synaptic functions,” he told us.

Simply put, a reduction in NO slows down the movement of nerve impulses across the connections between nerve cells, which can cause cognitive decline.

Scientists have long known that a healthy lifestyle can boost brain health. One 2015 paper suggests that exercise, intermittent fasting, and critical thinking are essential for optimal brain health throughout life.

Another large-scale study found that a healthy lifestyle is associated with slower memory decline in adults with normal cognition.

Positive experiences, such as social interaction, physical exercise and cognitive training are also good cognitive health. What is not known is how exactly these lifestyle factors have their effect.

Now, the one Aging study, carried out in mice, has found a mechanism that can explain how these positive experiences benefit your cognitive health.

The researchers put adult and elderly mice in an enriched environment for 10 weeks. They were housed in groups of eight to 10 mice, in large cages with bedding, a cardboard tube, a running wheel, several plastic toys (tunnels, platforms, seesaws), and a metal ladder. The toys were moved around twice a week, and new toys introduced once a week.

The control group was housed in standard cages, in groups of two to four mice, with only bedding and a cardboard tube.

Once a week, the researchers used land and water mazes to test the cognitive function of both groups. They tested the following:

Mice that had been housed in the enriched environment had improved performance on all behavioral tasks compared to those in the normal environment. This improvement was particularly marked in the older mice.

“Our study provides a potential mechanistic basis for the effects of enrichment—this removes the ‘woollyness’ associated with such enrichment studies and puts them on a more rigorous scientific basis,” said the corresponding author. Prof. Bruno FrenguelliProfessor of Neuroscience in the School of Life Sciences at the University of Warwick, UK.

The researchers did not see the benefits of mice with a mutation in MSK1 — an enzyme involved in neuronal proliferation and synaptic plasticity.

They concluded that MSK1 is required for the full benefit of enrichment of cognitive abilities, synaptic plasticity and gene expression.

Prof. Frenguelli told us how it works:

“MSK1 is an enzyme that, when activated, regulates gene expression – that is, it promotes the switching on of a large number of genes. A number of these genes have been implicated in various forms of learning and memory, so we think , that MSK1 exerts its beneficial effects on cognition by turning on these genes.”

“While our mechanistic studies were performed in mice, previous studies have shown that aging causes a reduction in nitrosylation of CaMKII in both mice and humans. (…) It should be possible to use pharmacological treatments that will increase the nitrosylation of CaMKII. ​CaMKII and thereby alleviate the cognitive deficits associated with normal aging,” Dr. Bayer said. MNT.

Although such treatments are not yet available, research is underway that Dr. Bayer explained: “This requires further research/development, but there are indeed candidate approaches – such as inhibitors of GSNOR, an enzyme that limits nitric oxide bioavailability and is more highly expressed with aging.”

But the second study shows that we may not need to wait for pharmacological treatments to delay cognitive decline. Prof. Frenguelli explained why lifestyle enrichment should work in humans as well as in mice.

“A key brain growth factor (BDNF), which activates MSK1, has been implicated in both rodents and humans as being important for these benefits,” he noted.

“(By) identifying key molecules involved in this process, this provides opportunities to explore and exploit these molecules as drug targets,” he added.

And, he advised, you’re never too old to benefit from exercise, social interactions and cognitive stimulation: “Our latest findings show that these benefits occur even in very old mice (equivalent to the 70s in humans), meaning , that it is never too late to offer and participate in such enrichment activities for older people.”