_Rats & ‘Senior Moments’

Surprisingly, few animal models exist to study HIV infection or antiretroviral therapies on the aging brain. Barry Waterhouse, a professor in neurobiology and anatomy at Drexel, hopes to address that pressing concern through the development of a robust rat model.

_Barry Waterhouse

Waterhouse is a professor of neurobiology and anatomy and vice dean of biomedical graduate and postgraduate studies

Researchers think the mix of drugs used to treat HIV/AIDS or the progression of the disease itself is causing inflammation and neurotoxicity in the brain. While anyone growing older suffers cognitive lapses—those so-called senior moments—HIV/AIDS patients appear to experience exacerbated problems.

“While the disease is under control, they’re starting to experience these cognitive deficits,” Waterhouse says. “This is very debilitating, because they’re otherwise healthy and in the workforce but their decision-making processes are compromised.”

Many excellent tissue culture models exist to study these processes, but in vivo options are limited. Waterhouse’s two-year pilot project, funded with a starter grant of $275,000 from the National Institutes of Health, will adapt a rat model that his lab has used in its study of attention deficit hyperactivity disorder to instead look at cognitive skills in relation to HIV/AIDS and aging.

In this project, the rats, trained to do two tasks that involve the prefrontal cortex, are exposed to viral coat proteins, which envelope the virus itself. “The viral coat proteins are not themselves infectious,” Waterhouse says, “but when the virus invades the central nervous system, the proteins become distributed around the brain, and they can generate an immune response from the brain’s tissue. That, it’s believed, precipitates a series of events that leads to cognitive decline and neurotoxicity.”

Two types of attention, sustained and flexible, are being measured.

To evaluate sustained attention, the rats are trained for 2.5 months in a behavioral chamber to recognize whether a dim light that appears for a mere 15 seconds is on or off. If it is on, the rat presses one lever and gets a water reward. If it is off, it presses another lever for its reward.

To measure flexible attention, the rats are trained on a set of rules to retrieve a food reward from a small clay flowerpot. Initially, the animals are trained to key into odor. Once mastered, the odor linked to the reward is changed. Once this new rule is mastered, the reward link is again changed, this time to the digging media in the pot or the textured surface surrounding the pot.

The viral coat protein—gp120 was selected as the most likely culprit—is introduced via surgery into the ventricular system of the brain.

Animals, both adult and aged, will be tested on the cortex dependent behavioral tasks both before and after the infusion of gp120.

Very preliminary results show that adult animals with gp120 have flexible attention deficits, Waterhouse says. “They’re slower to change their behavior patterns,” he says.