article
Green tea extract protects against brain damage in new mouse model of HIV-related dementia
Contact: Anne DeLotto Baier
abaier@health.usf.edu
813-974-3300
University of South Florida Health
Tampa, FL (May 1, 2007) -- A compound derived from green tea greatly
diminished the neurotoxicity of proteins secreted by the human
immunodeficiency virus, suggesting a new approach to the prevention
and treatment of HIV-associated dementia, also known as AIDS dementia
complex. The disorder is the most severe form of HIV-related
neuropsychiatric impairment.
University of South Florida neuroscientist Brian Giunta, MD, reported
the findings May 1 at Experimental Biology 2007 in Washington, DC. His
presentation was part of the scientific program of the American
Society for Pharmacology and Experimental Therapeutics. The study was
conducted using a new mouse model for HIV-related dementia developed
by Dr. Giunta and Jun Tan, MD, PhD, director of the Neuroimmunology
Laboratory at the Silver Child Development Center, USF Department of
Psychiatry,
"These findings suggest that EGCG, the green tea-derived compound, may
represent a new and natural compound for the prevention and treatment
of this devastating disease," Dr. Giunta said.
"This is a very important finding in the prevention and treatment of
HIV-related dementia, which is usually observed in the late stages of
HIV disease," said Abdul S. Rao, MD, MA, DPhil, senior associate vice
president for USF Health and vice dean for research and graduate
affairs at the College of Medicine. "The neuroprotective effects of
EGCG, the green-tea extract, may offer an alternative to existing mono
or combination antiretroviral therapies that are known to have poor
central nervous system penetration."
HIV-associated dementia, a debilitating cognitive, emotional, and
physical disorder, affects 22 percent of HIV-infected adults and more
than half of HIV-infected children. Symptoms often begin with slight
changes in behavior, intellectual ability, memory, and muscle
coordination. Some patients experience depression-like symptoms such
as loss of appetite and motivation. Tasks requiring complex thinking
and high concentration become difficult, and motor skills gradually
deteriorate over time.
The highly active antiretroviral therapies used in developed nations
appear to slow the development of brain damage in patients with HIV-
related dementia, making it a protracted disorder rather than an acute
one. Unfortunately, these therapies neither cure nor prevent
development of HIV-associated dementia and several epidemiologic
studies indicate they increase the prevalence of the dementia.
Currently, no treatments specifically target this neuropsychiatric
disorder.
HIV-associated dementia is believed to be caused by the direct effects
of HIV upon the brain. The virus secretes proteins known as Tat and
gp120, which have direct toxic effects on the neurons. The proteins
also have indirect effects caused by the release of chemical
messengers known as cytokines, which interact with the HIV proteins to
cause death of the brain cells. High levels of these cytokines alone
also are toxic to the brain.
When healthy mice were given doses of the HIV proteins Gp120 and/or
Tat, in combination with a cytokine known as interferon-gamma, they
developed brain damage closely resembling that seen in HIV-associated
dementia in humans. Dr. Giunta said the finding may help explain the
cognitive and behavioral changes in individuals infected with HIV.
Dr. Giunta then used epigallocatechin-3-gallate (EGCG), the major
antioxidant derived from green tea, to break into this pathway of
neurotoxicity. He was successful both in cell studies and in studies
involving the new mouse model of the disease.
Cultured neurons from mice were exposed to EGCG before being given a
cocktail of the two neurotoxic HIV proteins and the toxic cytokine.
The green tea compound inhibited the ability of the cytokine to act
with the HIV proteins to cause death and damage of the neurons. In
further confirmation, the green tea compound also inhibited the
neurotoxic properties of these HIV proteins in the presence of the
cytokine in live mice.
###
Dr. Giunta's coauthors for the study presented at Experimental Biology
2007 were Demian Obregon; Hauyan Hou; Jin Zeng; Nan Sun; Veljko
Nikolic, MS; Jared Ehrhart; Douglas Shytle, PhD; Francisco Fernandez,
MD; and Dr. Tan. Previous USF studies have shown that EGCG prevented
Alzheimer's-like damage in the brains of mice.
Contact: Anne DeLotto Baier
abaier@health.usf.edu
813-974-3300
University of South Florida Health
Tampa, FL (May 1, 2007) -- A compound derived from green tea greatly
diminished the neurotoxicity of proteins secreted by the human
immunodeficiency virus, suggesting a new approach to the prevention
and treatment of HIV-associated dementia, also known as AIDS dementia
complex. The disorder is the most severe form of HIV-related
neuropsychiatric impairment.
University of South Florida neuroscientist Brian Giunta, MD, reported
the findings May 1 at Experimental Biology 2007 in Washington, DC. His
presentation was part of the scientific program of the American
Society for Pharmacology and Experimental Therapeutics. The study was
conducted using a new mouse model for HIV-related dementia developed
by Dr. Giunta and Jun Tan, MD, PhD, director of the Neuroimmunology
Laboratory at the Silver Child Development Center, USF Department of
Psychiatry,
"These findings suggest that EGCG, the green tea-derived compound, may
represent a new and natural compound for the prevention and treatment
of this devastating disease," Dr. Giunta said.
"This is a very important finding in the prevention and treatment of
HIV-related dementia, which is usually observed in the late stages of
HIV disease," said Abdul S. Rao, MD, MA, DPhil, senior associate vice
president for USF Health and vice dean for research and graduate
affairs at the College of Medicine. "The neuroprotective effects of
EGCG, the green-tea extract, may offer an alternative to existing mono
or combination antiretroviral therapies that are known to have poor
central nervous system penetration."
HIV-associated dementia, a debilitating cognitive, emotional, and
physical disorder, affects 22 percent of HIV-infected adults and more
than half of HIV-infected children. Symptoms often begin with slight
changes in behavior, intellectual ability, memory, and muscle
coordination. Some patients experience depression-like symptoms such
as loss of appetite and motivation. Tasks requiring complex thinking
and high concentration become difficult, and motor skills gradually
deteriorate over time.
The highly active antiretroviral therapies used in developed nations
appear to slow the development of brain damage in patients with HIV-
related dementia, making it a protracted disorder rather than an acute
one. Unfortunately, these therapies neither cure nor prevent
development of HIV-associated dementia and several epidemiologic
studies indicate they increase the prevalence of the dementia.
Currently, no treatments specifically target this neuropsychiatric
disorder.
HIV-associated dementia is believed to be caused by the direct effects
of HIV upon the brain. The virus secretes proteins known as Tat and
gp120, which have direct toxic effects on the neurons. The proteins
also have indirect effects caused by the release of chemical
messengers known as cytokines, which interact with the HIV proteins to
cause death of the brain cells. High levels of these cytokines alone
also are toxic to the brain.
When healthy mice were given doses of the HIV proteins Gp120 and/or
Tat, in combination with a cytokine known as interferon-gamma, they
developed brain damage closely resembling that seen in HIV-associated
dementia in humans. Dr. Giunta said the finding may help explain the
cognitive and behavioral changes in individuals infected with HIV.
Dr. Giunta then used epigallocatechin-3-gallate (EGCG), the major
antioxidant derived from green tea, to break into this pathway of
neurotoxicity. He was successful both in cell studies and in studies
involving the new mouse model of the disease.
Cultured neurons from mice were exposed to EGCG before being given a
cocktail of the two neurotoxic HIV proteins and the toxic cytokine.
The green tea compound inhibited the ability of the cytokine to act
with the HIV proteins to cause death and damage of the neurons. In
further confirmation, the green tea compound also inhibited the
neurotoxic properties of these HIV proteins in the presence of the
cytokine in live mice.
###
Dr. Giunta's coauthors for the study presented at Experimental Biology
2007 were Demian Obregon; Hauyan Hou; Jin Zeng; Nan Sun; Veljko
Nikolic, MS; Jared Ehrhart; Douglas Shytle, PhD; Francisco Fernandez,
MD; and Dr. Tan. Previous USF studies have shown that EGCG prevented
Alzheimer's-like damage in the brains of mice.