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Mental Decline Thwarted in Aging Rats


Dr. Andrew Pieper


NIMH Radio: Dr. Andrew Pieper of the UT Southwestern Medical Center explains how his team discovered a memory enhancing compound in living mice.


Time: 00:03:34 | Size: 3.32 MB
Speaker: Dr. Andrew Pieper
Description: NIMH Radio: Dr. Andrew Pieper of the UT Southwestern Medical Center explains how his team discovered a memory enhancing compound in living mice.

Dr. Pieper:  We make new neurons every day of our lives. So we were interested in how we might be able to modulate this process.

Announcer: Dr. Andrew Pieper is with the University of Texas Southwestern Medical Center. Funded in part by the National Institute of Mental Health, Dr. Pieper and his team engaged in research that could lead to the treatment of disorders that affect memory, such as Alzheimer’s Disease.  The research focused on how to strengthen the memory storing process in aging rats, with a particular molecule targeting the hippocampus structure in the brain.

Dr. Pieper:  So the hippocampus is a region of the brain that’s vital to learning and memory.  And what we wanted to do was to see would this molecule enhance the ability of animals to learn.

Announcer: Out of a thousand molecules screened in live mice, eight showed favorable effects. But one stood out, P7C3. 

Dr. Pieper:  They predicted that P7C3 would be readily able to cross the blood-brain barrier and it would be easily formulated for oral delivery.  So we wouldn’t have to be infusing it directly into the brain to study it.  And, sure enough, when we tried it, it worked really well.  The first animal model that we tested it in was a mouse that was genetically engineered to be deficient in hippocampal neurogenesis. It restored the structure of the hippocampus and it restored functioning within the hippocampus.

Announcer: The goal was to use the P7C3 compound to increase survival in the number of cells that allow us to form memories.

Dr. Pieper:  We make way more of these cells than we end up keeping. And so, what we first found was that our molecule is enhancing this 30 day process of neurogenesis  by promoting the survival of those cells – by preventing them from dying once they’ve been made.  So it’s not actually making more to begin with, it’s actually allowing more of the ones that are made to survive.

Announcer: In order to gauge the effects of this compound they needed to test how it affected memory in aging rats.

Dr. Pieper:  Normally as rats age, they lose this ability to form this type of memory.  And this is associated with a decrease in hippocampal neurogenesis.  So our hypothesis was that if we could prevent the decline of production of new neurons with aging, then we might preserve the ability of aging rats to learn. When we gave 16-month old rats P7C3 for two months, and then compared them with rats that received vehicle for the same period of time, the rats that got the P7C3 learned significantly better than the rats that didn’t. And then we looked in their brains after the behavioral study was done, we saw that the rats that learned better had also produced many many times more neurons in this region of the brain.

Announcer: In short, this treatment demonstrated a way to stem declining memory skills in animals through the P7C3 compound. And this research could lead to potential new developments in the treatment of people struggling with Alzheimer’s disease.