EMBARGOED FOR RELEASE: 1 DECEMBER 2000
Contact: Jacqueline Weaver
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203-432-8555
Yale University in the brain
Estrogen deprivation leads to death of dopamine cells in the brain
Estrogen deprivation leads to the death of dopamine cells in the brain,
a finding by Yale researchers that could
have implications for post-menopausal women.
The cells can be regenerated if estrogen is administered within 10 days,
but by 30 days, the cells appear to be
ermanently lost, said D. Eugene Redmond, Jr., professor of psychiatry
and neurosurgery at Yale School of
Medicine and director of the Neural Transplantation and Regeneration
Program. Redmond is co-investigator and
spokesperson about the study published in the December issue of The
Journal of Neuroscience.
The principal investigator was Csaba Leranth, M.D., professor of
obstetrics and gynecology and neurobiology.
"Without estrogen, more than 30 percent of all the dopamine neurons
disappeared in a major area of the brain that
produces the neurotransmitter, dopamine, " Redmond said. "This finding
is consistent with a lot of observations for
which there has been, until now, no explanation. The results of the
study shed light on why men, who have less
estrogen in their bodies and more androgen to antagonize it, are more
likely to develop Parkinson's Disease than pre-menopausal women, and why
post menopausal women are more likely then to develop the disease."
The discovery was made after the researchers removed the ovaries of
female monkeys, thereby depleting their bodies of estrogen and other
gonadal hormones. Within 10 days, key neurons in the brain that protect
against Parkinson's Disease disappeared.
Redmond said monkeys were used in the study because, unlike usual
laboratory animals, they have real menstrual cycles and many other close
similarities to humans. The researchers were interested in sexual
differences in dopamine neurons in the substantia nigra area of the
midbrain, whose destruction is associated with Parkinson's Disease and
dementia.
The researchers first sought to determine whether circulating estrogen
might have long term effects by altering the number of dopamine neurons.
The density of dopamine neurons was calculated in the substantia nigra
of intact male and female primates; in female primates whose ovaries had
been removed; and in female primates whose ovaries had been removed but
were receiving estrogen replacement therapy.
"After both 10 and 30 days of estrogen deprivation, apparently 30
percent of the total number of substantia nigra dopamine cells are
lost," Redmond said. "Furthermore, the density calculations showed that
brief estrogen replacement restores the density of the total number of
neurons in that area of the brain 10 days after the ovaries have been
removed, but not 30 days later."
"These observations show the essential role of estrogen in maintaining
the integrity of the nigral dopamine system involved in muscle control
and higher brain functions. It suggests a new prevention or treatment
strategy for patients at risk of Parkinson's disease and certain forms
of memory-impairing disorders,"he said. "This also provides another
rationale for estrogen replacement therapy for postmenopausal women.
Thirty percent is a very significant number of cells in this system.
Maintenance, restoration or loss of that many cells could make the
difference between severe parkinsonism and having no symptoms at all."
But Redmond cautioned that women should not use the results to make a
decision about estrogen replacement therapy until further studies look
at the effects on dopamine cells of much longer periods of estrogen
deprivation.
He said the researchers also want to see if much larger doses of
estrogen or other hormones administered at 30 days and beyond of
estrogen deprivation would resuscitate the cells. All of this must be in
the context of possible side effects of hormone replacement that women
should take into account in consultation with their doctors.
Other investigators were Robert Roth, professor of psychiatry and
pharmacology; John Elsworth, senior research scientist, psychiatry;
Frederick Naftolin, M.D., professor of obstetrics and gynecology and of
molecular, cellular and developmental biology, and Tamas Horvath,
associate professor of obstetrics and gynecology and neurobiology.
The study was carried out at the St. Kitts Biomedical Research
Foundation in the West Indies.
CONTACT:
Jacqueline Weaver
203-432-8555
Yale University
--
Judith Richards, London, Ontario, Canada
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