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HIV Life >> Living With HIV

ScotCharles
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Reged: 05/06/05
Posts: 924
Loc: Los Angeles
HIV and the brain - update
      12/13/08 08:59 AM

My neurologist at UCLA, Dr. Elyse Singer, has been warning since the mid 1990's that HIV's effect on the brain and nervous systems was a ticking timebomb. The meds never completely eradicate the virus from the body and never effectively cross the blood/brain barrier. A diagnosis of an undetectable viral load means that you have a viral load so low they cannot effectively estimate it, not that you have no virus in your body. Relentlessly, year on year, the virus does its dirty work on the brain and nervous systems.

HIV in the brain causes depression, for instance. Have you not noticed how many people on this site have problems with depression. Some of it is situational depression, that is to say they are depressed because they are HIV+. However, for some the depression is likely organic and caused by the virus.

Interestingly, Dr. Singer has found that HIV effects a part of the brain that processes sensory information, which for me explains why I become panicked or anxious in crowds and on freeways; and, as a result can no longer drive; however, with tranquilizers, I can now go out to movies and go shopping at the mall. The damage done by HIV to this part of the brain also explains why I behave inappropriately in public on occasion, again effectively treated with tranquilizers.

I don't mean to be alarmist, but everyone needs to educate their Infectious disease specialist to this research so that you can receive the medications you need. My symptoms are midway on the way to full blown dementia, but they are treated, for now, with 1000 mg of Depakote, 150 mg of Tofranil, 150 mg of Seroquel, 100 mg of Resperidone and 400 mg of Lyrica. I see my psychiatrist every two months for a tune-up on the meds.

Despite these meds I still have trouble with balance, weakness in my arms and legs, and coordination. None of which can be treated by medications and because of which I am confined to a wheelchair.

Read the following research article that discusses how HIV effects the brain and make certain your IDS knows about this research.

Knowledge is power,

ScotCharles


Researchers identify toehold for HIV's assault on brain

Scientists have unraveled in unprecedented detail the cascade of events that go wrong in brain cells affected by HIV, a virus whose assault on the nervous system continues unabated despite antiviral medications that can keep the virus at bay for years in the rest of the body.

The new research reveals key steps taken in the brain by Tat, a protein that is central to HIV's attack on cells called neurons. Researchers discovered the receptor that Tat uses to attack neurons, and they were able to reverse the effects of Tat in the laboratory by blocking the receptor.

The discovery of a major molecular player in the process opens up a new avenue for researchers to explore in their efforts to prevent or treat HIV's neurological effects, for which there is no currently approved treatment. Researchers say that much of the molecular action that underlies HIV's attack on the brain also occurs in other diseases, such as Parkinson's and Alzheimer's diseases, and that the results spell progress for those conditions as well.

The team from the University of Rochester Medical Center and other institutions published its results online Nov. 13 in the journal PloS One.

The powerful antiviral drugs that keep many HIV patients healthy for years don't completely eradicate the virus from the body, and in the brain, even the very low levels of that remain cause relentless damage. Scientists have observed that a large percentage of HIV patients – perhaps up to half – show evidence of neurologic disease from the virus,

"The current medications give many patients a new lease on life. But the virus is still taking a toll on the brain, even when the virus appears to be much less active elsewhere in the body," said the paper's corresponding author, neurologist Harris "Handy" Gelbard, M.D., Ph.D. of the University of Rochester Medical Center.

Gelbard was a newly minted pediatric neurologist embarking on his career when a good friend of his – a doctor with whom Gelbard had trained – became ill and died of AIDS in less than two years. His friend's struggle, and the severity of his neurological symptoms, touched Gelbard. Gradually, with the support of mentors, Gelbard came to focus on the neurological effects of HIV. He now leads a group of researchers funded by the National Institute of Mental Health that is trying to identify or create the first treatment for the neurological effects of HIV, known collectively as neuroAIDS or HIV dementia.

Scientists have known that Tat, which helps HIV operate, replicate, and infect cells, is at the forefront of HIV's attack on the brain, bringing about severe inflammation. Immune cells within the brain go into overdrive, churning out substances that attract more immune cells, and white blood cells from the body flood in and join the fray, all clumping together to form destructive entities known as multinucleated giant cells.

"Suddenly the brain environment turns from nurturing to toxic, and the brain has to work much harder to send messages. Cells are on overdrive, spending a lot more energy to do the same things they used to do easily," said Gelbard, who is director of the Center for Neural Development and Disease at Rochester.

Other changes occur throughout the brain as well. Neurons that normally reach throughout the brain by forming networks of far-reaching, delicate extensions crucial for cell communication become damaged. Instead of sprouting healthy dendrites – projections that resemble tiny trees – neurons in the brain of an HIV patient have had parts of their dendrites abruptly torn off, in a process known as "synaptic pruning." The dendrites begin to look like a patch of severely damaged trees after a bad ice storm.

Such damage occurs in parts of the brain crucial for thinking, decision-making, and movement and memory. That accounts for symptoms like difficulties concentrating, forgetfulness, poor coordination, confusion, and gait disturbances. In later stages, neuroAIDS can cause outright dementia.

Gelbard's team discovered that Tat works through the ryanodine receptor to sicken neurons in two ways. Scientists have known that Tat makes vulnerable the mitochondria, organelles within neurons and other cells that are commonly considered the "power packs" or energy sources for cells. The team discovered that Tat destroys the ability of mitochondria to protect themselves from changes in levels of calcium.

The scientists discovered another effect of Tat as well. Tat has a dramatic effect on an organelle known as the endoplasmic reticulum, where proteins are actually assembled and folded. Gelbard's team discovered that it's Tat's effects on the ryanodine receptor that cause an "unfolded protein response" seen in the brains of HIV patients. Shape is everything for proteins, and they're nearly always useless or harmful when they are unfolded or misfolded. The problem in HIV patients is exacerbated because protein folding requires a great deal of energy – energy that cells whose mitochondria are petering out aren't likely to have.

The team also showed, in mice, that a single exposure to Tat has long-lasting effects on the brain, causing problems with mitochondria and endoplasmic reticulum weeks later. Perhaps most striking, Gelbard says, is the observation that the exact same types of damage were seen in brain tissue of patients with HIV and neurologic disease but not in tissue from patients with HIV who did not have the neurologic disease.

The findings are in line with past findings from the team, which has shown that the central problem in HIV dementia is not that brain cells simply die. Rather, they become sick and lose their ability to communicate with each other. Because the cells are still alive, there is hope that the condition could be stopped or even reversed with proper treatment. Indeed, doctors commonly see patients who begin antiviral therapy and immediately are less confused and have improved brain functioning, but the effect generally fades as the disease progresses.

In their experiment, Gelbard's team was able to stop the harmful effects of Tat in neurons from mice by using the drug dantrolene, which blocks the ryanodine receptor. While the work offers a new target in the search for a drug that could be used in people to stop the effects of HIV dementia, Gelbard cautions that dantrolene has side effects and would not be appropriate.

"A lot of people are under the impression that HIV has been 'solved,' that somehow, it's no longer a problem. But the disease never went away, and it's a huge problem," said Gelbard, who is professor of Neurology, Pediatrics, and Microbiology and Immunology.

"There are a fair number of similarities between this brain disease and other diseases, such as Parkinson's or Alzheimer's," said Gelbard. "We hope that what we are learning can be applied to other diseases as well."

###

The first author of the paper is former graduate student John P. Norman, Ph.D., now with Exxon-Mobil. Other authors were Seth Perry, Ph.D., research assistant professor of Neurology; graduate students Holly Reynolds and Michelle Kiebala; Sanjay Maggirwar, Ph.D., and Stephen Dewhurst, Ph.D., professors of Microbiology and Immunology; Karen De Mesy Bentley; David Volsky, Ph.D., of Columbia University Medical Center; and Margarita Trejo and Eliezer Masliah, M.D., of the School of Medicine at the University of California at San Diego.



--------------------
Life is a river.
Carpe diem.

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Entire thread
Subject Posted by Posted on
* HIV and the brain - update ScotCharles 12/13/08 08:59 AM
. * Re: HIV and the brain - update BrokenWingedBird   01/25/09 09:06 AM
. * Re: HIV and the brain - update ScotCharles   01/26/09 10:18 AM
. * Re: HIV and the brain - update DOFORYOU   01/19/09 06:54 AM
. * Re: your special supplement for Scott BrokenWingedBird   01/20/09 06:56 AM
. * Re: your special supplement for Scott DOFORYOU   01/21/09 01:55 PM
. * Re: your special supplement for Scott ScotCharles   01/26/09 10:23 AM
. * Re: your special supplement for Scott BrokenWingedBird   01/25/09 08:58 AM
. * Re: your special supplement for Scott DOFORYOU   01/30/09 07:17 AM
. * Re: your special supplement for Scott BrokenWingedBird   02/06/09 06:59 AM
. * Re: your special supplement for Scott DOFORYOU   02/07/09 10:12 AM
. * Re: your special supplement for Scott BrokenWingedBird   01/30/09 09:50 AM
. * Re: HIV and the brain - update JerryMc   12/22/08 08:45 PM
. * Re: HIV and the brain - update seanboi   12/22/08 04:20 PM
. * Re: HIV and the brain - update Btony   12/14/08 08:17 PM
. * Re: HIV and the brain - update BrokenWingedBird   12/13/08 10:04 AM
. * Re: HIV and the brain - update Btony   12/14/08 08:22 PM
. * Re: HIV and the brain - update BrokenWingedBird   12/15/08 04:42 AM
. * Re: HIV and the brain - update ScotCharles   01/03/09 11:11 AM
. * Re: HIV and the brain - update BrokenWingedBird   01/04/09 07:10 AM
. * Re: HIV and the brain - update ScotCharles   01/09/09 09:25 AM
. * Re: HIV and the brain - update BrokenWingedBird   01/11/09 06:39 AM
. * Re: HIV and the brain - update ScotCharles   01/12/09 10:32 AM
. * Re: HIV and the brain - update sick_of_fuckwits   01/26/09 10:11 AM
. * Re: HIV and the brain - update Jbeil111969   12/24/08 07:08 PM
. * Re: HIV and the brain - update ScotCharles   01/13/09 08:44 AM
. * Re: HIV and the brain - update ScotCharles   01/11/09 03:35 AM
. * Re: HIV and the brain - update BrokenWingedBird   12/25/08 05:51 AM
. * Re: HIV and the brain - update ScotCharles   01/03/09 11:17 AM
. * Post deleted by Becky AIDS2HIV   12/17/08 08:27 AM
. * Re: HIV and the brain - update BrokenWingedBird   12/18/08 06:09 AM
. * Re: HIV and the brain - update sick_of_fuckwits   01/27/09 06:20 AM
. * Re: HIV and the brain - update BrokenWingedBird   01/27/09 01:47 PM
. * Re: HIV and the brain - update sick_of_fuckwits   01/27/09 02:19 PM
. * Re: HIV and the brain - update BrokenWingedBird   01/28/09 05:16 AM
. * Re: HIV and the brain - update cunta_stalwart   01/28/09 05:44 PM
. * Re: HIV and the brain - update sick_of_fuckwits   01/28/09 05:49 PM
. * Re: HIV and the brain - update cunta_stalwart   01/28/09 06:01 PM
. * Re: HIV and the brain - update sick_of_fuckwits   01/28/09 06:15 PM
. * Re: HIV and the brain - update ScotCharles   01/28/09 12:56 PM
. * Re: HIV and the brain - update sick_of_fuckwits   01/28/09 05:46 AM

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