Navigation Links
AIDS interferes with stem cells in the brain
Date:8/15/2007

(La Jolla, CA August 15, 2007) A prominent problem in AIDS is a form of dementia that robs ones ability to concentrate and perform normal movements. Scientists at the Burnham Institute for Medical Research (Burnham) have discovered how HIV/AIDS disrupts the normal replication of stem cells in the adult brain, preventing new nerve cells from forming. Drs. Stuart Lipton, Marcus Kaul, Shu-ichi Okamoto and their colleagues uncovered a novel molecular mechanism that inhibits stem cell proliferation and that could possibly be triggered in other neurodegenerative diseases as well. These findings were made available to medical researchers today through priority publication online by the journal Cell Stem Cell.

A normally functioning adult human brain has the ability to partially replenish or repair itself through neurogenesis, the proliferation and development of adult neural progenitor/stem cells (aNPCs) into new nerve cells. Neurogenesis can take place only within specific regions of the brain, such as the dentate gyrus of the hippocampus.

The hippocampus is the brains central processing unit, critical to learning and memory. aNPCs differentiate, adapt, and assimilate into existing neural circuits and mature with guidance from neurotransmitters, the chemical substances that nerve cells use to communicate with one another. The brains self-renewal through neurogenesis is impaired in AIDS dementia, Alzheimers, Huntingtons, and other neurodegenerative diseases, as evidenced by a greatly reduced number of aNPCs in brain tissue from individuals suffering from these diseases. The Burnham team focused on the determining the effect of a protein associated with AIDS, called HIV/gp120, which plays a key role in the pathogenesis of AIDS dementia.

In initial work with cell cultures in Petri dishes, the researchers methodically ruled out the possibility that HIV/gp120 would be inducing the death of stem cells and determined instead that HIV/gp120 was acting by inhibiting stem cell proliferation. Next, they confirmed these results in a special mouse strain bred to express HIV/gp120 in its brain. This mouse model for AIDS dementia mimics several features of the disease process found in humans. They observed a significant decrease in the number of proliferating stem cells in the brains of HIV/gp120-mice compared with similar tissue from normal, wild-type mice.

HIV/gp120 is known to interact with two receptors, called chemokine receptors, which are expressed on aNPCs. The researchers discovered that the same two receptors were targeted by HIV/gp120 sourced from either mouse or human brain tissue.

In search of a mechanism behind the finding that HIV/gp120 reduced proliferation of aNPCs, the scientists studied the effect of the protein on the cell cycle. Cells undergo seasons or cycles, known as G1, S, G2, and M (for mitosis, or cell division). They found that cells exposed to HIV/gp120 got stuck in the G1 or resting phase, and that the cell cycle was arrested.

Cell cycle is studied intensively by cancer researchers who have delineated certain checkpoint pathways that can jam cell proliferation, one of the key behaviors of cancer. Checkpoint pathways are overcome by cancers when they fool the bodys normal machinery into producing more cancerous cells. With dementia, it turns out that the opposite is true: the Burnham team discovered that HIV/AIDS could co-opt the checkpoint pathway to prevent stem cells in the brain from dividing and multiplying.

One such checkpoint pathway is modulated by an enzyme called p38 mitogen-activated protein kinase (MAPK), whose activity is known to disrupt the cell cycle. In mature nerve cells, the Burnham team had previously shown that HIV/gp120 activates the p38 MAPK pathway to contribute to cell death. Lipton and colleagues now report that the p38 MAPK pathway is also the mechanism underlying decreased stem cell proliferation in the brain associated with HIV/AIDS. Under experimental conditions, they were able to neutralize the p38 MAPK pathway and restore stem cell proliferation.

We show for the first time how HIV/AIDS inhibits proliferation of neural stem cells and prevents the formation of new nerve cells in the adult brain, said Dr. Stuart Lipton, Director of Burnhams Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research.

The fact that the mechanism of action involves the p38 MAPK enzyme is fortuitous because drugs to combat that pathway are being tested for other diseases. If they prove effective, they might also work to protect the brain. Thus, this study offers real hope for combating the bad effects of HIV/AIDS on stem cells in the brain. Lipton went on to state, It will be important to see if HIV/AIDS acts similarly on stem cells for other organs in the human body, as this may impact on the disease process as a whole.


'/>"/>

Contact: Nancy Beddingfield
nbeddingfield@burnham.org
858-646-3146
Burnham Institute
Source:Eurekalert

Related biology news :

1. How hot emotional brain interferes with cool processing
2. Wisconsin scientists grow critical nerve cells
3. Jump-starting T Cells In Skin Cancer
4. Spleen may be source of versatile stem cells
5. Researchers discover way to make cells in the eye sensitive to light
6. Priming embryonic stem cells to fulfill their promise
7. Lack of enzyme turns fat cells into fat burners
8. Poor prenatal nutrition permanently damages function of insulin-producing cells in the pancreas
9. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
10. Elusive HIV shape change revealed; Key clue to how virus infects cells
11. Mouse brain cells rapidly recover after Alzheimers plaques are cleared
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/15/2016)... 15, 2016 Research and ... Biometrics Market 2016-2020,"  report to their offering.  , ... , ,The global gait biometrics market is expected ... the period 2016-2020. Gait analysis generates ... be used to compute factors that are not ...
(Date:4/13/2016)...  IMPOWER physicians supporting Medicaid patients in ... standard in telehealth thanks to a new partnership with ... IMPOWER patients can routinely track key health measurements, such ... and, when they opt in, share them with IMPOWER ... local retail location at no cost. By leveraging this ...
(Date:3/31/2016)... March 31, 2016  Genomics firm Nabsys has completed ... Barrett Bready , M.D., who returned to the ... original technical leadership team, including Chief Technology Officer, ... Development, Steve Nurnberg and Vice President of Software and ... company. Dr. Bready served as CEO of ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... June 24, 2016  Regular discussions on a range of ... between the two entities said Poloz. Speaking at ... Ottawa , he pointed to the country,s inflation target, ... government. "In certain ... institutions have common economic goals, why not sit down and ...
(Date:6/23/2016)... ... June 23, 2016 , ... UAS LifeSciences, one of ... their brand, UP4™ Probiotics, into Target stores nationwide. The company, which has been ... Target to its list of well-respected retailers. This list includes such fine stores ...
(Date:6/23/2016)... MA (PRWEB) , ... June 23, 2016 , ... ... Peel Plate® YM (Yeast and Mold) microbial test has received AOAC Research Institute ... platform of microbial tests introduced last year,” stated Bob Salter, Vice President of ...
(Date:6/23/2016)... ... , ... STACS DNA Inc., the sample tracking software company, today announced that ... joined STACS DNA as a Field Application Specialist. , “I am thrilled that ... of STACS DNA. “In further expanding our capacity as a scientific integrator, Hays brings ...
Breaking Biology Technology: