New Drug May Help Rescue The Aging Brain

["M.Schild" <mmoo@xxxxxxxxxxxxxxxx>]

New Drug May Help Rescue The Aging Brain
ScienceDaily (Mar. 31, 2008) â As people age, their brains pay the price â 
inflammation goes up, levels of certain neurotransmitters go down, and the 
result is a plethora of ailments ranging from memory impairment and 
depression to Alzheimerâs and Parkinsonâs. 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 Î- 
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 compoundâs short-term 
effects, Alfred E. Mirsky Professor Bruce McEwen and his lab members made a 
far longer commitment: The scientists studied the drugâs 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.
âNobody had ever looked at the long-term effects of these ampakines on the 
aging brain,â says McEwen, head of Rockefellerâs 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 â the brainâs 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 rodentsâ 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. âEvery marker we chose to look at seemed to indicate 
there was some preservation of function during aging with chronic treatment,â 
Hunter says. The drug appears to slow agingâs 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 â itâs 
the chemical that helps you get up off the couch and socialize or exercise. A 
severe loss of dopamine production causes Parkinsonâs disease, âso this drug 
has the potential, perhaps, to block the progression of the disease,â Hunter 
says.
Not only that, but it could be helpful for much less severe conditions, too. 
As people age, itâs often harder for them to feel motivated to socialize or 
even eat, leading to depression and making latent conditions worse. âSo maybe 
this drug isnât going to be the one that prevents Parkinsonâs,â Waters 
says, âbut maybe itâs 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.â
With such a variety of impacts on neurotransmitters, S18986 holds enormous 
potential. But so far, itâs only potential. The researchers hope to dig 
deeper to find out precisely how the drug works. âThereâs a lot to be done,â 
Hunter says, âand this shows that thereâs broad potential for these 
compounds.â
Reference: Experimental Neurology 210(1):109â117 (March, 2008)

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