How Estrogen Can Lead to Memory Loss

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Have you ever wondered how the brain creates a memory?

How the brain creates our consciousness?

It turns out that long protein polymers tube-shaped structures within the brain do the job.

Called microtubules, like any other cellular structure, it’s possible to interfere with these structures.

That interference leads to memory loss and potentially worse consequences.

And some drugs and hormones actively inhibit microtubule formation.

One thing that interferes with microtubules is estrogen.

It inhibits their formation, and explains the relationship between estrogen and dementia.

And these are not haphazard structures and are made up of identical repeating subunits.

Anything that interferes with their formation affects how they function.

These microtubules exist in many places in the body, including neurons, the eye, mitochondria, and in nerves.

As early as 1975, researchers started publishing articles hypothesizing the role of microtubules in nerve conduction and consciousness.

In fact, they are the only biological structure which appears capable of quickly transmitting information.

The secret to this protein’s conductivity probably lies in its orderly formation.

It contains fluorescent tryptophan and histidine residues in the center of the tube.

The fluorescence emits a blue light when excited.

This allows it to transfer the energy to another tryptophan, which can likewise pass it to another.

This energy transfer happens very quickly.

In fact, energy transfer is routinely used to measure the tryptophan to tryptophan distance in proteins.

To do this, scientists irradiate proteins with polarized light and measure the light emitted by the tryptophan.

Since the energy moves at a specific rate, they can use this rate and the amount of light detected in their calculations.

Then they can calculate the spacing between the tryptophan molecules.

In 1960, Weber first demonstrated that nonradiative electronic energy transfer could occur between tyrosine and tryptophan molecules free in solution as well as in proteins.

This is the most plausible manner of long-distance nerve transmission.

So microtubules are extremely important structures for this reason.

The body uses microtubules to allow different parts of the body to communicate quickly.

The brain contains a lot of microtubules, and they can be found traveling down the optic nerve.

These most likely guide light down the center of the tubules, into the brain.

Unfortunately, many drugs and hormones are very effective at inhibiting the formation of these very important structures.

One of the most damaging is the gout medication called colchicine.

Scientists are so familiar with this effect that they use it when studying microtubule formation.

Another favorite drug for this research is Taxol.

But this study looks at colchicine.

Dr. Margolis did hundreds of individual experiments with different concentrations of drugs to see what he could figure out.

He found that it required very low concentrations to inhibit microtubule formation.

Not much at all.

Just one individual molecule of colchicine was enough to affect how long a microtubule could grow.

The rest of the tubule will grow a bit, but it will rapidly lose stability.

This instability is probably why colchicine’s side-effects include nerve damage, memory loss, and muscle weakness.

A single colchicine-dimer complex can block the assembly of a microtubule.

And other studies show that microtubules are essential for memory and learning in rats.

Nakayama injected varying amounts of this drug (.01μg–2μg) into the brain of rats.

He started off very small and then escalated the doses.

He let the rats rest for a week and then gave them a battery of behavioral tests.

This researcher observed that the rats with the higher colchicine doses took longer to solve the mazes.

The low amount necessary for this effect isn’t surprising since just one molecule can inhibit the formation of an entire microtubule.

The mechanism(s) underlying these actions is unclear, but has been hypothesized to involve the microtubule-depolymerizing actions of this drug.

He also killed the rats and looked at their brains under a microscope.

He noticed severe structural changes that became more pronounced as doses escalated.

Microtubules seem essential for memory, and a dysfunction in tubule formation could lead to dementia.

There are other microtubule blocking agents, too.

The most important is estrogen — there is a relationship between hormones and memory loss.

Dr. D’Amato studied 16 molecules for their ability to inhibit microtubule polymerization.

He discovered that different forms of estrogen inhibited microtubule formation nearly as much as colchicine.

And the synthetic estrogen drug diethylstilbestrol (DES) was also a very effective inhibitor.

In fact, estrogen produces by products that also interfere.

Estrogen produces one powerful inhibitor called 2-methoxyestradiol.

An interesting point here is that testosterone can also produce 2-Methoxyestradiol.

Although men, in contrast, have an intrinsic supply of estrogen by having the ability to aromatize testosterone (aromatase) into estrogen in the brain.

Researchers looked at the molecules for colchicine and estrogen to try to figure out how they affect the microtubules.

The two molecules have similarities which may explain their impact.

They have similar ring structures, and both have a methoxy (CH₃O–) group in a similar location.

Brain plasticity requires it to produce new microtubule as necessary.

And anything that interferes with this process also affects the ability to learn.

Interestingly, researchers noted that Taxol actually increases microtubule formation.

So what to do now?

Start by avoiding things like aluminum, estrogen, colchicine, and other microtubule inhibitors.

Avoiding these should help to keep the brain flexible and active.

Also, make sure you get enough vitamin C — it helps stop the production of 2-methoxyestradiol.

Because COMT methylates the hydroxyl group of enediols, ascorbic acid acts as a competitive inhibitor.

You can also try aromatase inhibitors.

These can keep the body from turning androgens into estrogens in the first place.

 

 

Detection of Tryptophan to Tryptophan Energy Transfer in Proteins 
https://link.springer.com/article/10.1023%2FB%3AJOPC.0000016261.97474.2e?LI=true 

Conduction pathways in microtubules, biological quantum computation, and consciousness 
http://www.sciencedirect.com/science/article/pii/S0303264701001836 

2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site http://www.pnas.org/content/91/9/3964.full.pdf Involvement of microtubule integrity in memory impairment caused by colchicine 
http://www.sciencedirect.com/science/article/pii/S0091305701006347 

Mechanism of Colchicine-Dimer Addition to Microtubule Ends: Implications for the Microtubule Polymerization Mechanism 
http://pubs.acs.org/doi/pdf/10.1021/bi00565a014 
Click for more information on trypophan's effects, more information on slowing aging, and more information on colchicine's negative impact on memory.