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Mouse study offers new clues to cognitive decline
Date:5/8/2014

12 months," Stein said. "And at the higher dose, we saw a rescue of the neural stem cell pool in aged mice."

Imai called this finding exciting because it supports the possibility of a future NMN supplement.

"We think that NMN could convey a similar effect in people," Imai said. "A future clinical trial for NMN will tell us if it has any efficacy in humans."

In addition to maintaining stem cell populations and keeping the brain supplied with all its cell types, the investigators showed that NAD also is vital for the process of cognition itself.

Reporting in The Journal of Neuroscience, they showed that neurons of the mouse forebrain depend heavily on NAD in normal cognitive function. Instead of deleting Nampt in stem cells, this time Stein deleted it only in neurons of the forebrain. All other cells were normal, including those that make axon insulation.

Without Nampt and its eventual product, NAD, in forebrain neurons, the behavior of the mice changed dramatically, according to the investigators.

"The mice were really hyperactive, with a twofold increase in activity levels," Stein said. "They also showed a loss of anxiety-like behaviors. These mice didn't seem to sense or fear potentially threatening situations and showed fairly drastic memory defects."

Stein pointed out that these neurons are in a region of the brain known to be particularly vulnerable to neurodegenerative conditions from Alzheimer's disease to stroke.

"It's possible that these neurons' dependence on Nampt is responsible for their extreme susceptibility to these conditions," she said. "It would be interesting to model some of these diseases in mice and see if supplementing NMN provides any benefit to their behavior or memory."

"We haven't done that study yet," Imai added. "But this is the direction the entire field is going."


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Contact: Julia Evangelou Strait
straitj@wustl.edu
314-286-0141
Washington University School of Medicine
Source:Eurekalert  

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