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Nutrition and Brain Function,
Food for the Aging Mind
Scientists know that certain nutrients and other key chemical compounds
are essential to human brain function. Serious deficiencies in some of
these, such as vitamin B12 and iron, can lead to impaired cognitive
function due to neurological, or nerve fiber, complications.
Cognition can be defined as the ability to use simple-to-complex
information to meet the challenges of daily living.
So, could careful attention to diet help protect the aging brain from
problems with nerve cell signals involved in memory and cognition?
A clear-cut answer could greatly affect the 77 million baby boomers
who are now facing retirement. Their independence, quality of life,
and even economic status will largely be defined by their ability to
traffic information signals as they age.
In researching the nutrition-brain connection, new technologies are being
used, such as those that take images of the brain or actually count
individual brain cells. Behavioral tests that measure motor and cognitive
skills or lack thereof, are also providing insights. Yet the science of
nutrition and brain function is relatively new and evolving.
Agricultural Research Service scientists at several locations nationwide
are contributing to a growing body of research that explores the effect of
diet and nutrition on the brain and its function across the lifespan.
Boosting Neuronal Function
The brain's billions of neurons "talk" to one another through chemical
neurotransmitters that convey signals through neural pathways. These
chemical transporters, which include norepinephrine, serotonin, and
dopamine, are key to signal movement.
Although people naturally lose brain cells throughout their lives, the
process of neuronal death does not necessarily accelerate with aging.
"There is a lot of individual difference," says ARS neuroscientist James
Joseph. "Loss of mental agility may be less due to loss of brain cells
than to the cells' failure to communicate effectively."
Joseph heads the Neuroscience Laboratory at the Jean Mayer USDA Human
Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston.
There, researchers are looking at the beneficial effects of certain dietary
plant compounds to learn how they affect brain function.
"Vitamins and minerals in plant foods provide protective antioxidants,"
says Joseph. But fruits, vegetables, nuts, seeds, and grains contain
thousands of other types of compounds that contribute significantly to
the overall dietary intake of antioxidants.
"A partial measure of the antioxidant effect is called 'ORAC,' for Oxygen
Radical Absorbance Capacity. ORAC scores are now showing up in charts and
on some food and beverage packages. They may be helpful in choosing foods
to include in your diet."
Perhaps there is no better place in which to gauge the power of
antioxidants than between the minute connections of the nerve cells.
Bucking Long-Held Dogma
Eight years ago, Joseph and colleagues began publishing a series of
studies, done in rodents, that shed light on the relationship between
various diets and the mechanisms behind cognitive losses in specific
neighborhoods of the aging brain.
Many in the series are groundbreaking in that they challenge the
long-accepted belief that the central nervous system, which includes
the brain, is not capable of regenerating itself. Other published studies
in the series echo similar findings based on primate and human brain
research at the Salk Institute for Biological Studies, San Diego,
California. Scientists there, using new technologies, disputed the notion
that the brain does not make new neurons - a process called
"neurogenesis" - into old age: It does, but at a much slower rate.
One of the first of Joseph's studies, published in the Journal of
Neuroscience, showed a protective effect of consuming antioxidants.
Study rats were fed, from adulthood to middle age, vitamin E, strawberry
extracts, or spinach extracts, all with similar ORAC values. Animals
receiving the high-antioxidant diets did not experience the age-related
cognitive performance losses seen in control rats fed standard chow.
A later study, also published in the Journal of Neuroscience, showed a
reversal of functional loss among rats on special diets. Each of three
groups of rats, equivalent in age to 63 year-old humans, was fed a different
high-antioxidant extract. A control group was fed standard chow.
After 8 weeks-equivalent to about 10 years in humans-the rats' performance
levels were measured.
The rats fed the spinach, strawberry, or blueberry extracts effectively
reversed age-related deficits in neuronal and cognitive function.
In addition, the blueberry-fed group far outperformed their peers while
traversing a rotating rod to test balance and coordination.
"Despite their status as 'senior citizens,' those rats showed remarkable
stamina on neuromotor function tests," says psychologist and coauthor
Barbara Shukitt-Hale, also with the Neuroscience Laboratory.
Examination of the brain tissue of those blueberry-fed rats showed much
higher levels of dopamine than were found in the other groups. Dopamine
has many functions within the brain. In particular, it can affect the way
the brain controls movements.
"We suspected that the combined antioxidant potency of compounds in
blueberry extract may have reduced inflammatory compounds in the brains
of these older animals," says Joseph. "Inflammation ordinarily contributes
to neuronal and behavioral shortfalls during aging."
Tests have since shown that blueberry compounds cross the blood-brain
barrier and localize in rodent brain tissue.
Hard News: Brain Plaques
Later, the lab's researchers published an Alzheimer's disease model study
in Nutritional Neuroscience. They studied mice that carried a genetic
mutation for promoting increased amounts of amyloid beta, a protein
fragment found within the telltale neuritic plaque, or "hardening of
the brain," seen in Alzheimer"s disease.
Although the exact cause of Alzheimer's is not completely understood,
experts have recently identified one mechanism involving the insufficient
breakdown and recycling of amyloid protein in the brain. That mechanism is
both genetic and physiological. In those individuals, normally harmless
amyloid protein turns into fragments of amyloid beta, which build up as
plaque in the brain rather than being escorted into cellular recycling.
That action leads to cell death and weakened neuronal communication.
In the mouse study, beginning at age 4 months-early adulthood-half the
brain-plaqued group was fed a diet that included blueberry extract for
8 months. The other half was fed standard rat chow and so was a control
group of mice that didn't carry the amyloid-plaque mutation.
At 12 months-early middle age-all groups were tested for their
in a maze.
The brain-plaqued mice that were fed the blueberry extract performed as
well as the healthy control mice and performed much better than their
brain-plaqued peers fed standard chow.
A look at the plaqued brains of both the blueberry-fed and chow-fed mice
after death revealed no difference in the number of brain plaques in
either group. "Amyloid-beta-induced plaques are only one aspect of
Alzheimer's disease," says Joseph. "But the fact that we saw a diet-induced
behavioral difference, despite a similarity in plaque density in both
these animal groups, is significant."
The team found increased activity of a family of enzymes called "kinases"
in the brains of the amyloid-plaqued mice that were fed blueberry extract.
Two kinases found in particular, ERK and PKC, are important in mediating
cognitive function, such as converting short-term memory to long-term.
"These kinase molecules are involved in signaling pathways for learning
and memory," says Joseph. "It could be that the increased kinase activity
within the plaque-ridden brains of the blueberry-fed mice enhanced the
signaling in certain receptors."
Brain Cells Are Born
Another HNRCA rat study looked at the aged brain's ability to change
physiologically-a condition scientists refer to as "neuronal plasticity."
In addition to cell division and differentiation, or "mission assignment,"
brain tissue undergoes many other changes throughout aging.
For example, a newborn sprouts billions of nerve cells while soaking up
information from the environment. But lower levels of synapse growth
continue in waves throughout the lifespan. Little-used synapses are
eliminated, while others are strengthened in a neuronal pruning process,
Repair mechanisms involve neural immune cells, called "microglia," that
seek to heal and protect injured brain tissue; enzymes that regulate safe
chemical levels; and genes that are expressed in response to inflammation.
The neuronal-plasticity study investigated the physiological link between
nutrition and the memory-control hippocampal area of the aged brain. That
region, in the center of the brain, is essential for what's called "working"
or "short-term" memory. It receives and processes data, and then, if
needed, passes it on for storage.
Neurogenesis also plays a role in the formation of new memories. The
capacity of the hippocampus to produce new neurons is thought to be greatly
diminished during aging. But this study suggested that old rats fed
blueberry extracts for a short time had increased neurogenesis in the
dentate gyrus area of their brain's hippocampus. The dentate gyrus is
one of the few regions of the brain where neurogenesis occurs.
"We found changes in the proliferation of neurons in blueberry-fed rats,"
said Gemma Casadesus, formerly a graduate student with the Neuroscience
Laboratory and now with Case Western Reserve University. In maze tests,
blueberry-fed aged lab rats showed improvement in cognition over chow-fed
peers. "There was an association between the proliferation of neuronal
precursor cells and better performance of spatial memory," she says.
The researchers don't yet know whether the cognitive improvements seen in
the aged blueberry-fed rats translate to humans. "But it's an important
step in learning about the brain's ability to rescue itself from
age-associated declines in physiological function," Casadesus says.
Can You Hear Me Now?
Neurons that can't get their messages through signaling pathways are
cell phones that can't get their signals through to other cell phones.
Why does this happen?
As the brain matures, cell division becomes largely restricted to
specific regions of the brain, and brain cells tend to become more
vulnerable to two partners in crime: oxidative stress and inflammation.
In the body, free radicals-weakened atoms formed during activities of daily
living-are missing an electron and want to bond with neighboring
biomolecules to stabilize. The problem is that unless neutralized,
free radicals cause cellular damage known as "oxidative stress."
Cellular antioxidant defense systems counterbalance these rogue molecules,
but they're not 100 percent effective-particularly as the body and brain
mature. And the brain is thought to be especially vulnerable to oxidative
"Weighing just 3 pounds, the brain accounts for only 2 percent of the
body's total mass, yet it uses up to half of the body's total oxygen
consumed during mental activity," says Joseph. "Phytochemicals, together
with essential nutrients in foods, provide a health-benefits cocktail of
sorts. It is feasible that continued research in this area will point to
dietary regimens that are effective in boosting neuronal function."
Inflammation is thought to be stoked by the overactivation of microglia-the
neural immune cells mentioned earlier.
Microglia are usually dormant, but they migrate to the site of any brain
injury. These sentries make up about 20 percent of the cell population in
certain regions of the brain.
While seeking to protect and repair tissue, microglia cells produce and
send out molecular stress signals, some by way of defensive cytokines, as
a bugle call to other cells. Those signals begin a cascade of reactions,
including the activation of genes that express proteins and other stress
chemicals to help clear away cellular debris.
Microglial activation by amyloid beta is thought to be a key event in the
progression of Alzheimer's disease. "When microglia are stuck in an
always-on loop in response to plaque buildup in the brain, they become
problematic in and of themselves," says Joseph.
This year, Francis Lau, a molecular biologist in the Neuroscience
Laboratory, published a study that investigated whether blueberry
extracts could have a preventive effect on inflammatory signals coming
from activated microglia cells.
Microglial activation is considered the hallmark of inflammation in the
central nervous system. For this study, Lau used a rodent microglial cell
line that has previously served as a model to study plaque-induced
Lau exposed groups of those test cells to various levels of blueberry
extracts. He then challenged the cells with oxidative stress by exposing
them to a toxin-lipopolysaccharide-that triggers secretion of inflammatory
Neuroinflammation has been linked to the expression of genes that spew two
inflammatory enzymes, iNOS and COX-2, and two cytokines, IL-1b and TNF-a.
Lau used real-time PCR (polymerase chain reaction) to find and measure
expression of genes that produce iNOS and COX-2 in the stress-induced cell
cultures. He found that the blueberry treatment significantly reduced that
The blueberry extract also markedly lessened secretion of the two
inflammatory cytokines. In fact, says Lau, "In cells exposed to the
highest blueberry extract concentration, the amount of TNF-a cytokine
found was next to nothing-essentially identical to that found in the
Looking to the Future
The food industry is now using a range of new and existing product
ingredients to gain entrance into the emerging brain-health market. Some
are producing food labels that list ORAC values-for example, for use on
containers of polyphenol-rich fruit juices and teas. So far, however,
there has been no review conducted by the U.S. Food and Drug Administration
on health benefits from eating berries.
Future studies at HNRCA will ideally include use of new diagnostic tools
as well as human clinical trials. Neuroimaging equipment, for example,
could be used to monitor the influence of various dietary factors on
development of plaque within the human brain. Such studies aim to find
the best dietary regimens to help adults preserve their mental capabilities
This research is part of Human Nutrition, an ARS national program (#107)
described on the World Wide Web at www.nps.ars.usda.gov.
James A. Joseph is with the USDA-ARS Human Nutrition Research Center
on Aging at Tufts University, Boston, MA.
Source: "Nutrition and Brain Function" was published in the August 2007 issue of
Agricultural Research magazine, by Rosalie Marion Bliss, Agricultural Research Service
Adapted by Editorial Staff, September 2007
Last update, August 2008