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Chad A. Mirkin, Northwestern University, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences. Photo by Bill Arsenault. 

DNA Blueprints Guide The Construction Of Specific Human Structures

Chad Mirkin discusses using DNA to build a three-dimensional structure out of gold, likening the process to building a house. Starting with basic materials such as bricks, wood, siding, stone and shingles, a construction team can build many different types of houses out of the same building blocks.
 
The article includes an audio recording of the full interview. Photo courtesy of the UCSD School of Medicine.
Chronic Estradiol Exposure And Impaired Working Memory Print E-mail
Medicine - Hormones & Meds
TS-Si News Service   
Thursday, 07 August 2008 16:30
Memory Blur
TS-Si Hormones & Meds
Adana, Turkey and Cambridge, UK. Scientists have long been known that a specific hormonal signal from the hypothalamus switches on the system that controls sex hormone production from the ovaries and testis. Turning on the sy...
Almondsbury, Bristol, UK. A report released by CHEM Trust provides hard data on how chemicals in the environment have harmed male fish, amphibians, reptiles, birds and mammals. These findings highlight the widespread feminisa...
London, UK. Researchers have called for more studies into the practice of forcing psychiatric patients to take medication after a review showed that there have been very few rigorous investigations of the procedure.  &n...
San Francisco, CA, USA. A quarter of drug trials submitted in support of new drug applications to the US Food and Drug Administration (FDA) remain unpublished five years after the fact, says new research published in the jour...
Blomington, UN, USA. Researchers continue to accumulate evidence of a complex interplay between a female's brain and her hormones. While a woman's brain and body may need female hormones for proper functioning, it is also kno...
Amsterdam, The Netherlands. Individuals who have a sexually transmitted disease (STD) and women with yeast and bacterial vaginal infections have an increased risk of becoming infected with HIV if they are exposed to the virus...
Ann Arbor, MI, USA. Women with depression may be much more likely than men to get relief from a commonly used, inexpensive antidepressant drug, a new national study finds.   But many members of both se...
Urbana, IL, USA. The main estrogen in the female body is estradiol. Doctors often prescribe Hormone Replacement (HT) regimens that only mimic the effects of estradiol, such as conjugated estrogens an...
Urbana, IL, USA. The main estrogen in the female body is estradiol. Doctors often prescribe Hormone Replacement (HT) regimens that only mimic the effects of estradiol, such as conjugated estrogens and other substances. Other women rely on phytoestrogens from plants that only approximate the effects of estradiol.
 
Both approaches have effects that vary from dangerous to ineffective and lack the direct — and safer — dosages available from actual estradiol preparations. Even though the relative safety of estradiol has been established, are there other effects that should be considered?
 
Effects of Chronic Estradiol Treatment on Delayed Spatial Alternation and Differential Reinforcement of Low Rates of Responding. Victor C. Wang, Helen J. K. Sable, Young H. Ju, Clinton D. Allred, William G. Helferich, Donna L. Korol, and Susan L. Schantz. Behavioral Neuroscience 122(4) 794–804. doi: 10.1037 / a0012513.
 
Researchers at the University of Illinois report that chronic exposure to estradiol can diminish some cognitive functions. Rats exposed to a steady dose of estradiol were impaired on tasks involving working memory and response inhibition, the researchers found. Their report appears in the journal Behavioral Neuroscience.
 
The researchers made the discovery when studying the effects of estradiol on activities mediated by the prefrontal cortex, a brain region that is vital to working memory and to the ability to plan, respond to changing conditions and moderate or control one's behavior.
 
(L) Susan L. Schantz, a University of Illinois professor of veterinary biosciences and principal investigator on the study.; (R) Neuroscience graduate student Victor Wang, the study's lead author.
(L) Susan L. Schantz, a University of Illinois professor of veterinary biosciences and principal investigator.; (R)  Neuroscience graduate student Victor C. Wang, the lead author. Photo by L. Brian Stauffer.
 
Working memory is the ability to briefly remember information needed for a particular task, says Susan Schantz. An example in humans is a phone number that is forgotten soon after the number is dialed. "With working memory you're just keeping it active until you use it."
 
The investigators had not expected to see such pronounced results. In fact, the study originally had been designed to give them baseline information for a separate inquiry into the effects of soybean estrogens on cognitive function.
 
They planned to compare the effects of chronic estradiol exposure to the effects of chronic exposure to genistein, a phytoestrogen found in soybeans. Genistein is believed to have similar, but not exactly equivalent, effects in the body as natural or synthetic estrogens. However, no study has definitively proven this to be so.
 
In the new study, rats were trained to press one of two levers to obtain a food reward.
  • Those that alternated between the levers (which were withdrawn from the rat enclosure for a few seconds between trials) received a reward. Those that hit the same lever twice in a row got no reward.
     
  • Rats exposed to estradiol performed worse than their counterparts on this task, earning significantly fewer rewards.
A second set of tests measured the rats' ability to wait before responding to a stimulus.
  • The rats had to wait 15 seconds before pushing a lever to get a reward.
     
  • Those exposed to estradiol performed worse on this task than those that were not exposed.
"That's the test where we really saw the most striking effects with estradiol," Schantz said. The estradiol-treated rats "were not as good at waiting," she said.
 
"Rats treated with estradiol are definitely a lot more active and make a lot more lever presses," said neuroscience graduate student Victor C. Wang, the study's lead author. "That's not conducive toward being rewarded."
 
Schantz and her colleagues had focused on the prefrontal cortex because it is rich in estrogen receptor beta (ER-beta), a protein that spurs gene expression and other activities in the cell when it binds to estradiol. Genistein also activates ER-beta.
 
Some women take genistein supplements or eat soy-based foods to reduce hot flashes or other symptoms of menopause, Schantz said. "Women take them thinking they'll be a safe alternative to hormone-replacement therapy and they might help hot flashes," she said. Those who have heard that hormone replacement can improve cardiac or brain function also hope that eating soy or taking genistein supplements will have the same effects, she said.
 
The effects of hormone replacement therapy (HRT) are more complex – and problematic – than once thought. Large-scale studies of the effects of hormones generally use conjugated estrogen preparations and synthetic progestins (e.g., medoxyprogesterone). These are problematic substances when compared to the relative safety of estradiol and nd a true progestin (e.g., prometrium.
 
The recent results of hormone studies using conjugated estrogen preparations and synthetic progestins have not been encouraging. A recent large-scale study of HRT in post-menopausal women was stopped because of an increased risk of stroke and blood clots in women taking estrogen alone, and a higher than average incidence of breast cancer, cardiovascular disease, blood clots and stroke in women taking estrogen and progesterone.
 
Studies of estrogen's effects on cognition have also had mixed results. In earlier studies, for example, psychology professor Donna L. Korol, a collaborator on the current project, found that estradiol enhances some abilities, such as place or spatial learning, while hindering others, such as learning that relies on stimulus-response associations, considered by some to be akin to "habit" and not fluid thought.
 
Performance in these tasks involves brain structures outside the prefrontal cortex.
 
The research indicates that multiple factors influence the effects of estradiol on the brain, Schantz said. The timing of the exposure, the types of brain functions or structures studied and the age of the test subjects can all generate different results, she said.
 


Effects of Chronic Estradiol Treatment on Delayed Spatial Alternation and Differential Reinforcement of Low Rates of Responding. Victor C. Wang, Helen J. K. Sable, Young H. Ju, Clinton D. Allred, William G. Helferich, Donna L. Korol, and Susan L. Schantz. Behavioral Neuroscience 122(4) 794–804. doi: 10.1037 / a0012513.

Abstract

Estrogens have been shown to both enhance and impair cognitive function depending on several factors, including regimen of hormone treatment, age of subject, and task attributes. In rodent models, estradiol tends to enhance spatial learning and impair response or cued learning, but effects on executive functions are less well-studied. In this experiment, spatial working memory and response inhibition were tested using delayed spatial alternation (DSA) and differential reinforcement of low rates of responding (DRL) tasks in ovariectomized rats that were given chronic estradiol via Silastic implants resulting in serum estradiol concentrations of 86.2  8.2 (SEM) pg/ml. Rats were tested for 25 days DSA with variable delays of 0, 3, 6, 9, and 18 seconds between lever presentations, followed by 30 days on a DRL-15s operant schedule. Estradiol-replaced rats showed a significantly lower proportion of correct responses on the DSA task compared to vehicle-implanted ovariectomized animals. On DRL, estradiol -treated rats showed a lower ratio of reinforced to nonreinforced presses. These data suggest that chronic estrogen exposure may impair rats’ abilities on measures of executive function including working memory and response inhibition.

 
TS-Si News ServiceThe TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. The sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.
 
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Last Updated on Friday, 08 August 2008 12:52