Solving the puzzle of cognitive problems caused by HIV infection

(Press-News.org) July 1, 2011 – (Bronx, NY) – A longstanding medical mystery – why so many people with HIV experience memory loss and other cognitive problems despite potent antiretroviral therapy – may have been solved by researchers at Albert Einstein College of Medicine of Yeshiva University. Their findings are published in the June 29 issue of The Journal of Neuroscience.

Even though antiretroviral treatment suppresses HIV replication and slows the progress of HIV disease, between 40 and 60 percent of HIV-infected people eventually develop mild-to-moderate neurological deficits, and up to 5 percent develop full-blown dementia. Until now, researchers have not been able to explain why these complications, collectively known as neuroAIDS, occur.

In a previous study, the Einstein researchers found that HIV infects about 5 percent of brain cells known as astrocytes. These cells bolster the blood-brain barrier, a network of blood vessels that prevents harmful substances from crossing into the brain from the bloodstream. In the present study, the researchers show that even this low-level of astrocyte infection can profoundly damage the blood-brain barrier.

"The relatively few infected astrocytes emit toxic signals through specialized channels that kill neighboring uninfected astrocytes, ultimately weakening the blood-brain barrier and allowing harmful compounds to enter the brain," said senior author Joan Berman, Ph.D., professor of pathology and of microbiology & immunology at Einstein.

The evidence came from a laboratory model of the blood-brain barrier constructed of human cells and from examining brain tissue of macaque monkeys infected with the simian form of HIV. The results suggest that drugs capable of reducing the damaging signaling cascades triggered by HIV-infected astrocytes might help in preventing or treating neuroAIDS.

### The Journal of Neuroscience paper is titled "Human Immunodeficiency Virus Infection of Human Astrocytes Disrupts Blood–Brain Barrier Integrity by a Gap Junction-Dependent Mechanism." The paper's lead author is Eliseo Eugenin, Ph.D., assistant professor of pathology at Einstein.

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2009-2010 academic year, Einstein is home to 722 M.D. students, 243 Ph.D.students, 128 students in the combined M.D./Ph.D. program, and approximately 350 postdoctoral research fellows. The College of Medicine has 2,775 fulltime faculty members located on the main campus and at its clinical affiliates. In 2009, Einstein received more than $155 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five medical centers in the Bronx, Manhattan and Long Island - which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein - the College of Medicine runs one of the largest post-graduate medical training programs in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.einstein.yu.edu