Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

AIDS interferes with stem cells in the brain

17.08.2007
Discovery links mechanism for HIV/AIDS dementia, possibly other neurological disorders, with known cancer 'checkpoint' pathway

A prominent problem in AIDS is a form of dementia that robs one’s 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 brain’s 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 brain’s self-renewal through neurogenesis is impaired in AIDS dementia, Alzheimer’s, Huntington’s, 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 body’s 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 Burnham’s 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.”

Nancy Beddingfield | EurekAlert!
Further information:
http://www.burnham.org

Further reports about: Aids HIV/AIDS HIV/gp120 Lipton MAPK Stem aNPCs dementia nerve cells neurodegenerative disease p38 p38 MAPK pathway proliferation

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>