New drug may help rescue the aging brain

March 28, 2008
New drug may help rescue the aging brain
Age on the brain. An experimental drug, S18986, seems to counteract numerous symptoms of aging in rats. Animals given the drug daily for four months were active, with better memories and less inflammation in their brains. Dopamine-producing neurons in the forebrain of an 18-month-old drugged rat (top) are far more active than those in a normal rat of the same age.

As people age, their brains pay the price — inflammation goes up, levels of certain neurotransmitters go down, and the result is a plethora of ailments ranging from memory impairment and depression to Alzheimer’s and Parkinson’s. But in a long-term study with implications to treat these and other conditions, researchers have found that an experimental drug, taken chronically, has the ability to stem the effects of aging in the rat brain.

The drug, temporarily designated S18986, interacts with AMPA (short for α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, or ampakine) receptors in the brain. These receptors transmit excitatory signals in the brain, and researchers were interested in experimental AMPA-receptor drugs (such as S18986) for their neuroprotective abilities and for the way they temporarily boost memory.

But rather than investigating the compound’s short-term effects, Alfred E. Mirsky Professor Bruce McEwen and his lab members made a far longer commitment: The scientists studied the drug’s impacts on middle-aged to elderly rats and found that, when administered daily over four consecutive months, it appeared to improve memory and slow brain aging.

“Nobody had ever looked at the long-term effects of these ampakines on the aging brain,” says McEwen, head of Rockefeller’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology. Short-term studies, he notes, had shown that the drug appears to improve aspects of memory, likely by temporarily ramping up AMPA receptors in the hippocampus — the brain’s memory and learning center. But McEwen, research assistant Erik Bloss and postdocs Elizabeth Waters and Richard Hunter found that, over the course of four months, S18986 changed the entire profile of the older rodents’ brains.

When compared to control animals that had received only sugar water, the drugged rats were not only more active and better at memory tests, but their brains showed physical signs of slowed aging. Neurons in the forebrain that produce acetylcholine, a neurotransmitter known to play a role in learning and memory, had 37 percent less decline. Dopamine-producing neurons, which are responsible for sustaining activity and motivation levels, slowed their decline by 43 percent. Levels of inflammation in the brain were also significantly lower. “Every marker we chose to look at seemed to indicate there was some preservation of function during aging with chronic treatment,” Hunter says. The drug appears to slow aging’s effects throughout the entire brain.

Dopamine is a motivation- and movement-related neurotransmitter in the brain, and its presence is necessary for maintaining normal activity levels — it’s the chemical that helps you get up off the couch and socialize or exercise. A severe loss of dopamine production causes Parkinson’s disease, “so this drug has the potential, perhaps, to block the progression of the disease,” Hunter says.

Not only that, but it could be helpful for much less severe conditions, too. As people age, it’s often harder for them to feel motivated to socialize or even eat, leading to depression and making latent conditions worse. “So maybe this drug isn’t going to be the one that prevents Parkinson’s,” Waters says, “but maybe it’s going to improve the quality of life as you age, so that up until the very end of your life you can sustain that quality and sustain a higher activity level.”

With such a variety of impacts on neurotransmitters, S18986 holds enormous potential. But so far, it’s only potential. The researchers hope to dig deeper to find out precisely how the drug works. “There’s a lot to be done,” Hunter says, “and this shows that there’s broad potential for these compounds.”

Citation: Experimental Neurology 210(1):109–117 (March, 2008)

Source: Rockefeller University

Explore further: Forgoing chemo linked to worse survival in older patients with advanced colon cancer who had dementia

Related Stories

Forgoing chemo linked to worse survival in older patients with advanced colon cancer who had dementia

September 22, 2017
A pre-existing diagnosis of dementia was associated with increased risk of death for older patients with advanced colon cancer; however, some of the effects of dementia on survival could be mediated by receipt of chemotherapy.

Online dementia publication sheds light on latest research

September 21, 2017
More than 400,000 Australians live with dementia and that number is expected to climb to 1.1 million by 2056.

Intermittent electrical brain stimulation improves memory

September 7, 2017
Intermittent electrical stimulation of an area deep inside the brain that degenerates in Alzheimer's appears to improve working memory, scientists report.

Ketogenic diet improves healthspan and memory in aging mice

September 5, 2017
A ketogenic diet significantly improved memory in aging mice and increased the animal's chances of surviving to old age. Results of the study from Eric Verdin's lab at the Buck Institute for Research on Aging in Novato, CA ...

Memory decline after head injury may be prevented by slowing brain cell growth

September 15, 2017
The excessive burst of new brain cells after a traumatic head injury that scientists have traditionally believed helped in recovery could instead lead to epileptic seizures and long-term cognitive decline, according to a ...

New possibility of studying how Alzheimer's disease affects the brain at different ages

August 31, 2017
Alzheimer's disease can lead to several widely divergent symptoms and, so far, its various expressions have mainly been observed through the behaviour and actions of patients. Researchers at Lund University in Sweden have ...

Recommended for you

Researchers describe mechanism that underlies age-associated bone loss

September 22, 2017
A major health problem in older people is age-associated osteoporosis—the thinning of bone and the loss of bone density that increases the risk of fractures. Often this is accompanied by an increase in fat cells in the ...

Researchers develop treatment to reduce rate of cleft palate relapse complication

September 22, 2017
Young people with cleft palate may one day face fewer painful surgeries and spend less time undergoing uncomfortable orthodontic treatments thanks to a new therapy developed by researchers from the UCLA School of Dentistry. ...

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

Study finds immune system is critical to regeneration

September 20, 2017
The answer to regenerative medicine's most compelling question—why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot—may lie with the body's innate immune system, ...

Immune cells produce wound healing factor, could lead to new IBD treatment

September 20, 2017
Specific immune cells have the ability to produce a healing factor that can promote wound repair in the intestine, a finding that could lead to new, potential therapeutic treatments for inflammatory bowel disease (IBD), according ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.