Ampakine Prevents Loss of Dendrites in the Aging Rat Brain

The research community is very interested in loss of neural plasticity in the brain over the course of aging, a slowing of the introduction and integration of new neurons, and diminished pace of change in the connections between nerve cells. If aging is damage, then this is probably the tail end of a complicated chain of reactions to that damage. As seems to be the case for stem cell populations in other tissues, it is plausible that tinkering with signaling in brain tissue might be able to compensate for this loss, overriding some of this evolved reaction to damage without addressing the damage. The open question is the degree to which this approach can be effective; the evidence to date suggests it can produce large enough benefits in comparison to existing medicine to be worth trying, though if the underlying damage remains unrepaired, contributing to all of the other issues that accompany aging, then frailty and death is still inevitable.

As brain cells age they lose the fibers that receive neural impulses, a change that may underlie cognitive decline. Researchers recently found a way to reverse this process in rats. "There's a tendency to think that aging is an inexorable process, that it's something in the genes and there's nothing you can do about it. This paper is saying that may not be true." The researchers studied dendrites - the branch-like fibers that extend from neurons and receive signals from other neurons - in rats. Evidence from other studies in rodents, monkeys, and humans indicates that dendrites dwindle with age and that this process - called dendritic retraction - occurs as early as middle age.

The team wanted to know whether dendritic retraction was already underway in 13-month-old or "middle-aged" rats and, if it was, could they reverse it by giving rats a compound called an ampakine. Ampakines had previously been shown to improve age-related cognitive deficits in rats as well as increase production of a key growth factor, brain-derived neurotrophic factor (BDNF) in the brain. The researchers housed 10-month-old male rats in cages with enriched environments. Eleven rats received an oral dose of the ampakine each day for the next three months while the other 12 rats received a placebo. After three months the researchers examined an area of the rats' brains associated with learning and memory, the hippocampus, and compared that with the hippocampi of two-and-a-half-month-old or "adolescent" rats.

"Middle-aged" rats given the placebo had shorter dendrites and fewer dendritic branches than the younger rats. The brains of rats given the ampakine, however, were mostly indistinguishable from the young rats - dendrites in both were similar in length and in the amount of branching. What's more, the researchers also found that treated rats had significantly more dendritic spines, the small projections on dendrites that receive signals from other neurons, than either the untreated rats or the young rats. The researchers found that anatomical differences between the rats also correlated with differences in a biological measure of learning and memory: the treated rats showed enhanced signaling between neurons - a phenomenon called long-term potentiation. "The treated rats had better memory and developed strategies to explore."



Does anyone know which ampakine was used in the study?

Posted by: Santi at February 3rd, 2016 11:11 AM

it seems to me that I have found a page full of information about our conditions of aging. It is unusual to me to understand it but now I will start to accept that I need to accept that I will become older. Thanks for the insights also to push me to make an appointment with a Gerontologist.

Posted by: Ingrid Benitez at February 3rd, 2016 11:29 AM

Perhaps of interest --

Compound Found in Herbs and Spices Strengthens Brain Connections

'Cocktail' of compounds improves brain function in rodents

Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils

However, uridine must be used judiciously --

Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice

Posted by: Lou Pagnucco at February 3rd, 2016 12:58 PM

Corb from thinks it's CX614 and MonisPubis from r/Nootropics thinks it's CX614.

Posted by: Santi at February 3rd, 2016 7:57 PM

@Santi: I have access to the full version of the paper. The ampakine they used was CX929, given orally at a dosage of 5 mg/kg on a schedule of 5 days on / 2 days off. They also note that excessive amounts of ampakine (20+ mg/kg) produce agitation and then prodromal effects.

Posted by: James O'Donnell at February 16th, 2016 10:14 AM

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