January 19, 2008

Causes of Cognitive Losses in the Brain

Biochemist Donna Bielinski prepares mammalian tissue samples to look for the formation of new neurons, or neurogenesis. Photo courtesy of USDA, ARS

What causes the cognitive part of the brain to stop working?

Cognition can be defined as the mental process of knowing, including aspects such as awareness, perception, reasoning, and judgment and the ability to use simple-to-complex information to meet the challenges of daily living.

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. Dopamine has many functions within the brain. In particular, it can affect the way the brain controls movements.

Neurons that can’t get their messages through signalling pathways are like cell (mobile) phones that can’t get their signals through to other cell phones. 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 neighbouring biomolecules to stabilize. The problem is that unless neutralized, free radicals cause cellular damage known as “oxidative stress.”

Cellular antioxidant defence systems counterbalance these rogue molecules, but they’re not completely effective - particularly as the body and brain mature. The brain is thought to be especially vulnerable to oxidative stress.

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 Agricultural Research Service neuroscientist James Joseph. “Loss of mental agility may be less due to loss of brain cells than to the cells’ failure to communicate effectively.”

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 neighbourhoods 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 reiterate 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. The brain doesn't remain fixed after early development with damage being irreparable, but continues to change throughout a person's life, with damaged cells being repaired and new ones made but at a much slower rate as we age.

“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 Agricultural Research Service neuroscientist James 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.”

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.

The 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.

A rat study at the USDA Human Nutrition Research Center on Aging 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, of sorts.

While seeking to protect and repair tissue, microglia cells produce and send out molecular stress signals, some by way of defensive cytokines, as a 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.

Microglia cells are a part of the neuroglia, which in turn is part of the delicate connective tissue framework which supports the nervous matter and blood vessels of the brain and spinal cord.

Microglial activation by amyloid beta (mentioned above) 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 build-up in the brain, they become problematic in and of themselves,” says Joseph.

Microglial activation is considered the hallmark of inflammation in the central nervous system.

Future studies at Human Nutrition Research Center on Aging (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 while aging.

The link between nutrition and cognitive function is an area that has been largely overlooked in the past. But recent studies looking at the potential protective role of foods such as berries, green tea, and fish against cognitive impairment shows that this is slowly changing.

Adapted and modified from: “Nutrition and Brain Function” published in the August 2007 issue of Agricultural Research magazine. Rosalie Marion Bliss, Agricultural Research Service Information Staff. Photo courtesy of USDA, ARS. Used with permission.

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