Popescu Receives AHA Award to Extend Brain Receptor Research

The highly competitive award supports mid-career investigators with unusual promise and an established record of accomplishments pertaining to cardiovascular or cerebrovascular science.

For the last six years, Popescu, an associate professor of biochemistry, has researched the function and regulation of NMDA receptors, an important class of glutamate-activated brain receptors.

In June 2011, she received a $1.8 million grant from the National Institutes of Health (NIH) to continue investigating the fundamental properties of these receptors, whose functions are critical to memory, learning and awareness.

The objective of Popescu’s research is to find drugs that will allow NMDA receptors to perform functions essential to a healthy brain while diminishing or stopping signals that are toxic to brain cells in pathologies such as stroke, schizophrenia and neurodegenerative diseases, including Alzheimer’s.

Last year, Popescu’s group discovered a novel drug target for Alzheimer’s disease within NMDA receptors.

“Before drugs aimed at this target can become useful in the clinic, it is necessary to better understand how they affect basic brain functions,” Popescu explains. “This AHA award will help us initiate these investigations.”

The new award is intended to help Popescu expand her synaptic physiology research on NMDA receptors. Specifically, her group will attempt to validate in brain slices—a more physiologically relevant preparation—the findings they reported from their NIH-funded investigations.

To do this, they will test the hypothesis that distinct classes of drugs that modulate NMDA-receptor activity can “turn up or down” some biological functions carried by these receptors, without significant impact on other receptors.

In particular, they will exam the effects of:

• increased acidification of the synaptic environment as it occurs during stroke
• a glycine-site partial agonist called D-cycloserine, a drug used to alleviate some symptoms of schizophrenia
  
• pregnanolone sulfate, a naturally occurring neurosteroid

“These specific modulators have been selected based on the previous knowledge we obtained in the strictly controlled experimental conditions of a recombinant system,” Popescu says.

“The current grant allows us to test and hopefully validate these predictions in brain slices, a system that resembles more closely the conditions likely experienced by these receptors in vivo.”