Wednesday, June 27, 2007

Estrogen and the aging brain

As women advance in age, pregnancy and childbirth become increasingly dangerous and destructive. Perhaps to protect us, we women have evolved to be infertile later in life: our ovaries stop producing estrogen, causing our reproductive systems to gradually cease operations. Thus rendered barren, we can devote our maternal resources to mentoring and supporting our children and grandchildren. The rosy "grandmother hypothesis" is, however, not the only theory for the evolutionary origin of menopause.

The cessation of estrogen production also results in a number of debilitating symptoms, such as hot flashes, loss of short-term memory, and declining abilities to concentrate and learn new tasks, which would have put older women at greater risk for predation. Accordingly, some have hypothesized that menopause evolved as a way to "thin the herd," eliminating non-reproductive members of society and leaving food and other resources for the young. (Love you, Gumma!)

[This "culling agent" theory receives little support; the predominant theory as to why cognitive abilities decline is that conditions manifesting later in life (especially after reproductive age) are simply not subjected to the pressures of natural selection.]

Regardless of prehistorical reality, humans have evolved the propensity to thwart nature, creating the pharmaceutical industry and one of its many gifts: hormone replacement therapy (HRT). HRT does not rescue infertility, but is intended to mitigate the other lamentable effects of menopause, such as those impacting cognitive function.

The aging brain, while not suffering from notable cell death (except in conditions like Alzheimer's and Parkinson's Disease), is afflicted by significant changes in the connections (synapses) between neurons, within otherwise intact neural circuits. Certain molecules with essential roles in synaptic communication (e.g. glutamate receptors) change in quantity and location. These molecular changes are accompanied by significant structural alterations to the synapses themselves. Two regions display the greatest vulnerability to these changes: the prefrontal cortex (PFC), involved in attention and working memory, and the hippocampus, involved in many types of memory formation. Although these changes are inevitable concomitants of brain aging, they are exacerbated by the drop in estrogen levels experienced by women undergoing menopause, particularly in the PFC.

Estrogen, like all hormones, acts by traveling through the membrane of a cell to the nucleus, where it switches certain genes on or off, thereby regulating protein production. Of the many genes under the direct control of estrogen are the NMDA receptor (a key molecule for synaptic communication, in particular synaptic plasticity), elements of the cholinergic system (involved in attention and working memory), and genes that influence neuronal survival and structure. In particular, estrogen is known to enhance the number and strength of connections in the PFC of female rhesus monkeys which have had their ovaries removed ("ovariectomized," or OVX). The relevance to the human menopausal situation, however, involving both age and estrogen loss, was heretofore unknown.

A new study by John Morrison at Mt. Sinai School of Medicine investigated this issue by OVXing old and young rhesus monkeys, and treating half of each group with estrogen. The group then tested the monkeys on a task of short-term memory (STM), a component of working memory, in which the monkeys had to remember the location of an object after an increasing delay. They found that aged OVX monkeys which had not received estrogen treatment performed significantly worse than any of the other three groups (aged OVX + estrogen (E), young OVX + E, young OVX), indicative of significant cognitive decline. Moreover, the two groups of young animals performed equivalently, regardless of whether they received estrogen treatment, and the aged OVX + E group performed equally well as the former two. This surprising finding indicates that the estrogen treatment in the aged monkeys was sufficient to improve their cognitive function to levels comparable to their younger peers.

After cognitive testing, the researchers analyzed the brains of all monkeys, discovering that, in the PFC, estrogen increased synaptic density in both young and old OVX monkeys. Highest synaptic density was observed in young OVX + E monkeys, followed by comparable levels between young OVX and aged OVX + E, and lowest density in aged OVX without E. Moreover, estrogen treatment resulted in a significant increase in a particular subpopulation of synapses, which exhibit high dynamism and plasticity.

These findings indicate a complex interplay between estrogen and age, by which "young monkeys without [estrogen] can sustain excellent cognitive function against a background of dynamic spine plasticity." The one-two punch of age and estrogen loss, however, may be sufficiently destructive to impair an animal's cognitive function. By promoting the growth of new, dynamic synapses, estrogen may partially compensate for the effects of aging.

The implication with respect to HRT is that the timing of treatment is crucial. It may be important to begin treatment when ovarian hormone levels just begin to fall, at perimenopause, while synaptic plasticity mechanisms are still robust and resilient. Thus, this study contributes to the enormous body of HRT research (which currently consists of heaps of conflicting information). It has been suggested that the timing of hormonal intervention may underlie many of these contradictory data, and this study may lend some credence to this hypothesis and clear these cloudy waters.

Reference: Hao J et al. Interactive effects of age and estrogen on cognition and pyramidal neurosn in monkey prefrontal cortex. PNAS 2007 Jun 25 [Epub ahead of print].


Jake Young said...

This is an excellent post.

Two things...

1) John works next door to me and is a super nice guy. Try and meet him at SfN some time.

2) Just so you know, HRT is no longer recommended for anything other than short-term treatmnet of menopause. Look up the Women's Health Initiative in PubMed. Lots of doctors have been trying to spread the word on this because I don't think that people know.

Jake Young said...

...and I am an idiot because the discover article said just that about HRT.

Nevermind. :)

Anyway, I would emphasize that in spite of the positive memory consequences doctors are concerned about the cardiovascular effects enough to not usually be willing to prescribe HRT for that. (Also, HRT may increase stroke risk which would make Alzheimer's worse not better, so I am suspicious that it might ever be used to memory changes.)

Madam Fathom said...

Thanks Jake. The literature on HRT is undeniably confusing! There was just an article in NEJM that adds a little more coherence.

AlvaroF said...

Great article. Yes, women have a very difficult decision to make after menopause, with competing trade-offs and unclear guidance. I hope there's more research done to clarify what can help maintain cognitive abilities from a comprehensive health point of view.

宇韩 said...

wow gold
wow gold
eve isk
wow power leveling
wow power leveling
wow power leveling
wow power leveling
warhammer gold
warhammer power leveling
bestchina traveland
ghd straighteners

Cardi Ugg Boots
Classic Short Ugg Boots

Classic Tall Ugg Boots
Metallic Ugg Boots

Mini Ugg Boots
Sundance Ugg Boots

tiffany Jewelry

Anonymous said...

酒店喝酒,禮服店,酒店小姐,酒店領檯,便服店,鋼琴酒吧,酒店兼職,酒店兼差,酒店打工,伴唱小姐,暑假打工,酒店上班,酒店兼職,ktv酒店,酒店,酒店公關,酒店兼差,酒店上班,酒店打工,禮服酒店,禮服店,酒店小姐,酒店兼差,暑假打工,酒店經紀,台北酒店,禮服店 ,酒店小姐,酒店經紀,酒店兼差,寒假打工,酒店小姐,台北酒店,禮服店 ,酒店小姐,酒店經紀,酒店兼差,暑假打工,酒店小姐,台北酒店,禮服店 ,酒店小姐,酒店經紀,酒店兼差,寒假打工,台北酒店,禮服店 ,酒店小姐,酒店經紀,酒店兼差,暑假打工,酒店小姐,台北酒店,禮服店 ,酒店小姐,酒店兼差,暑假打工,酒店小姐,台北酒店,禮服店 ,酒店小姐,酒店經紀,酒店兼差,寒假打工,酒店小姐,台北酒店,禮服店 ,酒店小姐,酒店經紀,酒店兼差,暑假打工,酒店小姐,台北酒店,禮服店 ,酒店小姐,酒店經紀,酒店兼差,寒假打工,酒店小姐,台北酒店,禮服店 ,酒店小姐,酒店經紀,酒店兼差,暑假打工,酒店小姐,禮服店 ,酒店小姐,酒店經紀,酒店兼差,寒假打工,酒店小姐,禮服店 ,酒店小姐,酒店經紀,酒店兼差,暑假打工,酒店小姐,禮服店 ,酒店小姐,酒店經紀,酒店兼差,寒假打工,酒店小姐,禮服店 ,酒店小姐,酒店經紀,酒店兼差,暑假打工,酒店小姐,酒店傳播,酒店經紀人,酒店,酒店,酒店,酒店 ,禮服店 , 酒店小姐,酒店經紀,酒店兼差,暑假打工,招待所,酒店小姐,酒店兼差,寒假打工,酒店上班,暑假打工,酒店公關,酒店兼職,禮服店 , 酒店小姐 ,酒店經紀 ,酒店兼差,暑假打工,酒店,酒店,酒店經紀,酒店領檯 ,禮服店 ,酒店小姐 ,酒店經紀 ,酒店兼差,暑假打工, 酒店上班,禮服店 ,酒店小姐 ,酒店經紀 ,酒店兼差,暑假打工, 酒店上班,禮服店 ,酒店小姐 ,酒店經紀 ,酒店兼差,暑假打工, 酒店上班,酒店經紀

Anonymous said...

艾葳酒店經紀公司提供專業的酒店經紀, 酒店上班小姐,八大行業,酒店兼職,傳播妹,或者想要打工兼差打工,兼差,八大行業,酒店兼職,想去酒店上班, 日式酒店,制服酒店,ktv酒店,禮服店,整天穿得水水漂漂的,還是想去制服店日領上班小姐,水水們如果想要擁有打工工作、晚上兼差工作兼差打工假日兼職兼職工作酒店兼差兼差打工兼差日領工作晚上兼差工作酒店工作酒店上班酒店打工兼職兼差兼差工作酒店上班等,想了解酒店相關工作特種行業內容,想兼職工作日領假日兼職兼差打工、或晚班兼職想擁有鋼琴酒吧又有保障的工作嗎???又可以現領請找專業又有保障的艾葳酒店經紀公司!

一般的酒店經紀只會在水水們第一次上班和領薪水時出現而已,對水水們的上班安全一點保障都沒有!艾葳酒店經紀公司的水水們上班時全程媽咪作陪,不需擔心!只提供最優質的酒店上班,酒店上班,酒店打工環境、上班條件給水水們。心動嗎!? 趕快來填寫你的酒店上班履歷表

等相關服務 幫您快速的實現您的夢想~!!

Anonymous said...


raoliming2 said...

louis vuitton
replica handbags
balenciaga replica handbags
chanel replica handbags
chloe replica handbags
fendi replica handbags
gucci replica handbags
hermes replica handbags
louis vuitton replica handbags
miumiu replica handbags
prada replica handbags
ysl replica handbags
chanel replica handbags
gucci replica handbags
louis vuitton replica handbags
balenciaga replica handbags
chanel replica handbags
chloe replica handbags
fendi replica handbags
gucci replica handbags
hermes replica handbags
louis vuitton replica handbags
miumiu replica handbags
prada replica handbags
ysl replica handbags
replica handbags
replica handbags
fake designer handbags
discount replica handbags
replica handbags
replica handbags
replica handbags
designer replica handbags
replica handbags
replica handbags
replica handbags
fake replica handbags
fake replica handbags
replica handbags
replica handbags

Anonymous said...

vuitton replica
which are with handles should not be afraid on a angle of the wardrobe, autumn the louis replica
for a absolute continued time would be bigger off in a bolt louis vuitton replica
rather than a box.

太子 said...

If you have been looking for the right BEWITCHED to AVI converter that is powerful as well as customer friendly then you have certainly found one. It is not only easy to use BEWITCHED DVD but extremely convenient to. You will adore the speed at which it can go on to convert and diversify BEWITCHED DVD COLLECTION videos into video formats and at the most satisfactory of quality output possible.

lida can be put to use to reduce the effort that is required for reducing weight. You can easily reduce your body weight with the help of lida daidaihua that are available. There are slimming capsules that are making these products available. You can use the weight loss products with daidaihua for better and faster improvement in body weight. There are a number of ways of checking out the lida slimming that are available. You can take the help of the internet to check slimming capsule that are available.

kiara said...

Costa Rica Manuel Antonio Tours
Costa Rica Carara Biological
Arenal Volcano Costa Rica
Costa Rica Crocodile Aventure
Costa Rica Poas Volcano
Costa Rica Monteverde Tours
Costa Rica Sea Kayaking
Costa Rica Rafting
Costa Rica Atv Adventure
Costa Rica Tours Canopy
Costa Rica Rainforest Tour
Costa Rica Vacation Rentals
Costa Rica Groups Travel
Los Suenos Costa Rica Tours
Costa Rica Zip Line
Costa Rica Vacation Rentals
Costa Rica los Suenos Vacation Rentals
Costa Rica Wedding
Costa Rica los Suenos Fishing
Costa Rica los Suenos Condos
Costa Rica los Suenos Sportfishing
Los Suenos Resort
Costa Rica Whale Watching Tours
Costa Rica Dolphin Watching Tours
Costa Rica Dominical
Costa Rica Dominical Tours
Dominical Tours
Dominical Costa Rica Tours
Costa Rica DMC Incentive Travel

Anonymous said...

Anonymous said...

To be a good lenient being is to be enduring a philanthropic of openness to the far-out, an skill to group uncertain things beyond your own control, that can govern you to be shattered in uncommonly exceptional circumstances as which you were not to blame. That says something uncommonly outstanding thither the fettle of the righteous compulsion: that it is based on a conviction in the uncertain and on a willingness to be exposed; it's based on being more like a weed than like a jewel, something somewhat fragile, but whose mere precise attraction is inseparable from that fragility.

Anonymous said...

Advice in old age is foolish; for what can be more absurd than to increase our provisions for the road the nearer we approach to our journey's end.

office said...

Realizing he might have dug himself in there,Microsoft Office 2010the general emphasized that Office 2010he had spent some time as a junior Office 2007officer working "very closely Microsoft Officewith the Israeli air force" and that heMicrosoft Office 2007had found that "more cosmopolitan,Office 2007 key liberal version of the Israeli population" Office 2007 downloadto be just chock full Office 2007 Professionalof that sort of "goodwill" necessary Windows 7to give a bunch of land back Microsoft outlook 2010to the Palestinians.

xiamenb2c02 said...

Top quality of ecco shoes are developed for discerning customers.Enjoy a great selection of newest ecco shoes on sale,free

shipping,110% price guarantee.Top quality of ecco shoes is your best chooice

for daily life and working,sport,and so on.And hot sale now UGG Boots

.fashion on the outside,warm on the inside.

Anonymous said...

Getting rich is not the result of saving, or "thrift"; many very
penurious people are poor, while free spenders often get rich.
Later on in the same Century the new religion also worked hard to
change the custom of Blood-revenge. So, without spending any
money (assuming you already had a computer), you have your equipment.

my site :: free pdf ebook download