Alcoholism Changes Brain's Genetic Wiring

[neuro equipoise]

Excerpts: "Alcoholism Changes Brain's Genetic Wiring"

NEW YORK (Reuters Health) - Using the latest DNA technology, scientists
in Texas have found that alcohol abuse can alter genes in the brain.

Out of more than 4,000 genes analyzed in brain tissue, about 4% differed
by at least 40% between alcoholics and nonalcoholics, researchers report
in the December issue of the journal Alcoholism: Clinical and
Experimental Research.

``Just as a computer virus can change the programming of specific
functions, our data show that chronic alcohol abuse can change the
molecular programming and circuitry of the frontal cortex,创 the
study磗 lead author, Dr. R. Adron Harris, of the University of Texas
at Austin, said in a statement.

Most of the altered genes are related to white matter in the brain
called myelin. Since myelin forms a sheath around the brain's
communication cells, the genetic changes may help explain why alcoholics
have a higher risk of diseases that destroy myelin, according to the
researchers.


Harris and his colleagues used technology known as microarrays, which
allows scientists to view thousands of genes at once on a glass
microscope slide. The technology has made it much easier to see which
genes are expressed, or ``switched on.创

The investigators used two different microarrays to compare genes in a
brain region called the superior frontal cortex taken from 10 alcoholics
and 10 people who were either teetotalers or social drinkers.

``This study is a beginning to unraveling the undesirable changes in the
brain produced by chronic exposure to alcohol,创 Harris said. ``Such
studies will, eventually, result in new and better treatments for
alcoholism and other addictions.创

SOURCE: Alcoholism: Clinical and Experimental Research
2000;24:1873-1882.



Excerpt 2:

"Harris said all cells have exactly the same genes or deoxyribonucleic
acid (DNA). Different cells work differently because only some genes are
'turned on' in each cell, a process referred to as gene expression. RNA,
or ribonucleic acid, acts as a messenger, translating instructions from
DNA into the proteins that determine the appearance and function of each
cell. Drugs disrupt this normally well-regulated process.

"Alcohol can change gene expression in the brain. This is believed to be
responsible for many of the hallmarks of addiction, such as tolerance,
physical dependence and craving, as well as the consequences of chronic
alcoholism, such as neurotoxicity (brain damage)."

Harris said the challenge has been to find which genes are 'incorrectly'
turned on or off in the brains of human alcoholics because any of 50,000
genes may be important. Until the development of gene array technology,
it was impossible to analyze more than a handful of these genes."

http://www.sciencedaily.com/releases/2000/12/001225061856.htm

[G-A]

On Mon, 12 Jul 2004 14:09:25 -0400, NeuroEquipoise@webtv.net (neuro equipoise)
wrote:

>Excerpts: "Alcoholism Changes Brain's Genetic Wiring"

The usual incompetent joirnalism whenever it comes
to science and medicine...

>NEW YORK (Reuters Health) - Using the latest DNA technology, scientists
>in Texas have found that alcohol abuse can alter genes in the brain.

Alcohol does not "alter genes". It changes genes' expression.
That is, alters how active the genes are. But then - EVERYTHING
does it. Memory, immunity, ageing, exercise, etc, etc - all these
phenomena are in mutual casua relationships withj gene expression.
Briefly speaking, that's called LIFE. That's how life on Earth
works.

>Out of more than 4,000 genes analyzed in brain tissue, about 4% differed
>by at least 40% between alcoholics and nonalcoholics, researchers report
>in the December issue of the journal Alcoholism: Clinical and
>Experimental Research.

So, in reality what the authors did was to reveal that 4% of the
genes that are differenttially expressed in alcoholic subjects.
Which may be directly or indeirectly linked to alcohol abuse.
Valuable - yes. Has anything to do with what this article is
saying - no.

>``This study is a beginning to unraveling the undesirable changes in the
>brain produced by chronic exposure to alcohol,创 Harris said.

Unfotunately, we are still far away from being able to judge
"desirability" of any chnages in the brains we observe.
As far as gene expression vis-a-vis brain function goes,
the predictive power is still zero.

>Excerpt 2:
>
>"Harris said all cells have exactly the same genes or deoxyribonucleic
>acid (DNA). Different cells work differently because only some genes are
>'turned on' in each cell, a process referred to as gene expression. RNA,
>or ribonucleic acid, acts as a messenger, translating instructions from
>DNA into the proteins that determine the appearance and function of each
>cell. Drugs disrupt this normally well-regulated process.
>
>"Alcohol can change gene expression in the brain. This is believed to be
>responsible for many of the hallmarks of addiction, such as tolerance,
>physical dependence and craving, as well as the consequences of chronic
>alcoholism, such as neurotoxicity (brain damage)."
>
>Harris said the challenge has been to find which genes are 'incorrectly'
>turned on or off in the brains of human alcoholics because any of 50,000
>genes may be important. Until the development of gene array technology,
>it was impossible to analyze more than a handful of these genes."
>
>http://www.sciencedaily.com/releases/2000/12/001225061856.htm

This journo is much better. This study was in 2000. Arrays are now
routine (but expensive) thing. We are still totally in the dark
about brain function.

G-A

[neuro equipoise]

On - Mon, Jul 12, 2004, 5:57pm (EDT-1) ga@net (G-A) wrote:

>> Using the latest DNA technology, scientists in
>> Texas have found that alcohol abuse can alter
>> genes in the brain.

> Alcohol does not "alter genes".

>> "Harris said the challenge has been to find which
>> genes are 'incorrectly' turned on or off in the
>> brains of human alcoholics"


Excerpts:

"Vulnerability to complex diseases like alcoholism requires changes in
multiple genes. Because genetics studies indicate that between 40 and 60
percent of alcoholism vulnerability has a genetic basis (7), finding the
genes that are involved in alcoholism vulnerability is a high priority
for alcohol research. Genetics studies, such as the Collaborative Study
on the Genetics of Alcoholism, have already identified several sites in
the brain where the genes for alcoholism may be located."
http://www.niaaa.nih.gov/publications/aa48.htm


"There are two major application forms for the DNA microarray
technology: 1) Identification of sequence (gene / gene *mutation*); and
2) Determination of expression level (abundance) of genes."

"A mutation is any change of DNA material that can be reproduced. It can
occur at the level of the genome, chromosome or the gene itself. It is
this change which is responsible for so-called genetic disorders. Not
all mutations, however, produce disorders, as some remain unexpressed,
without noticeable effect on the organism.

Multifactorial diseases - Caused by mutations in several genes plus
environmental factors:

Common Examples: Alcoholism, heart disease"

[G-A]

On Wed, 14 Jul 2004 06:47:10 -0400, NeuroEquipoise@webtv.net (neuro equipoise)
wrote:

>On - Mon, Jul 12, 2004, 5:57pm (EDT-1) ga@net (G-A) wrote:
>
>>> Using the latest DNA technology, scientists in
>>> Texas have found that alcohol abuse can alter
>>> genes in the brain.
>
>> Alcohol does not "alter genes".
>
>>> "Harris said the challenge has been to find which
>>> genes are 'incorrectly' turned on or off in the
>>> brains of human alcoholics"
>
>
>Excerpts:

Do you ever talk yourself?

>"Vulnerability to complex diseases like alcoholism requires changes in
>multiple genes. Because genetics studies indicate that between 40 and 60
>percent of alcoholism vulnerability has a genetic basis (7), finding the
>genes that are involved in alcoholism vulnerability is a high priority
>for alcohol research. Genetics studies, such as the Collaborative Study
>on the Genetics of Alcoholism, have already identified several sites in
>the brain where the genes for alcoholism may be located."
>http://www.niaaa.nih.gov/publications/aa48.htm

The above is considered triusm and is not contested by anyone
sane anymore.

>
>"There are two major application forms for the DNA microarray
>technology: 1) Identification of sequence (gene / gene *mutation*); and
>2) Determination of expression level (abundance) of genes."
>
>"A mutation is any change of DNA material that can be reproduced. It can
>occur at the level of the genome, chromosome or the gene itself. It is
>this change which is responsible for so-called genetic disorders. Not
>all mutations, however, produce disorders, as some remain unexpressed,
>without noticeable effect on the organism.
>
>Multifactorial diseases - Caused by mutations in several genes plus
>environmental factors:
>
>Common Examples: Alcoholism, heart disease"

LOL. Yep, all correct, all general to the pint of being
meaningless and none of it says that alcohol "changes genes".
Ethanol is not mutagene - that much is very, very well
established. (Mutagene: a substance that causes physical
change(s) in the primary DNA sequence).

G-A

[Ron]

On Wed, 14 Jul 2004 10:20:41 -0500, G-A <ga@net> wrote:

> LOL. Yep, all correct, all general to the pint of being
> meaningless and none of it says that alcohol "changes genes".
> Ethanol is not mutagene - that much is very, very well
> established. (Mutagene: a substance that causes physical
> change(s) in the primary DNA sequence).

I don't think NE posted anything that claimed ethanol "changes genes";
only that ethenal can affect gene expression. Does knowing this cure
alcoholism? Nope. In fact, I don't think it will change anything about
what I do today, tommorrow, or the day after. I still think it's
interesting to know, though; and I'm glad people study that kind of
stuff. Nothing to get bent out of shape about...

Meaningless? I don't know about that. One of my favorite expressions
is "A journey of a thousand miles starts with a single step." Don't
write stuff off just cuz it ain't the whole enchilada.

I'm thinking about that expression a lot as I begin to paint my house.
I think I hate painting almost as much as I hate plumbing. Good thing
I'm not drunk up on a high ladder...

--
AB5DB9CC

[neuro equipoise]

On - Wed, Jul 14, 2004, 10:20am (EDT-1)
ga@net (G-A) wrote:

> Ethanol is not mutagene - that much is very, very
> well established. (Mutagene: a substance that
> causes physical change(s) in the primary DNA
> sequence).

Excerpt 1 -

"acetaldehyde, the initial metabolite of ethanol - is a recognized
mutagen and animal carcinogen

http://www.aje.oupjournals.org/cgi/content/full/159/1/1



Excerpt 2 -

"The major finding of this study is that alcohol causes an increase in
the mutagenicity of agents that damage DNA," said Deitrich. "This is as
a result of the metabolism of alcohol to acetaldehyde. In fact, it is
clear that acetaldehyde is the major culprit in the effects noted here."
*
The presumption is acetaldehyde itself causes the damage, but it could
be other aldehydes as well. For example, it may interfere with the
normal cellular mechanisms designed to inactivate endogenous aldehydes
produced in normal cellular function or those produced as a result of
alcohol's production of oxidative damage, Deitrich said.*
*
"The concept of acetaldehyde being a mutagen is not a novel concept and
the engineered cells produced a lot of acetaldehyde and these cells do
not have the ability to inactivate the acetaldehyde unlike cells in the
body," Boris Tabakoff, chairman of the department of pharmacology,
University of Colorado School of Medicine in Denver, told UPI. "It would
be more interesting to see if this happened under normal conditions in
how we live and not in engineered cells to see if it has broader
implications."
*
"An interesting next step in the research might be to add cigarette
smoke, which also contains acetaldehyde to the alcohol," he added.
*
Couch acknowledged the study did not uncover new ground but sets up
further research on DNA repair pathways and on the dose of acetaldehyde
that causes damage.*
*
"We speculate that alcohol in a limited dose does not impact on DNA
repair and that it has a beneficial impact on lipids in the body, hence
the studies on the beneficial effects of alcohol on the body," Qingyi
Wei, a molecular epidemiologist, at the MD Anderson Cancer Center at the
University of Texas in Houston, told UPI.*
***
"Alcohol has been known to inhibit folate absorption and folate helps
repair tissues from mutations -- that's why folate is needed both before
and in the first weeks of pregnancy to reduce the risk of birth
defects."*
*
Folate is a B vitamin found in a variety of foods and added to many
vitamin and mineral supplements as folic acid."

http://www.applesforhealth.com/HealthyFeatures/rexalcl3.html
*

[neuro equipoise]

Excerpt 3 - Acetaldehyde/gene mutations

"By far, the main source of exposure to acetaldehyde for the majority of
the general population is through the metabolism of alcohol. These
beverages contain ethanol, which is metabolized to acetaldehyde by
alcohol dehydrogenase (ADH). ADH activity has been detected in nearly
every tissue including liver, kidney, muscle, intestine, ovary, and
testes (Buehler et al., 1983; Agarwal & Goedde, 1990).

Cigarette smoke is also a significant source of exposure.

Acetaldehyde is taken up by red blood cells and, following ethanol
consumption in humans and in baboons, in vivo, intracellular levels can
be 10 times higher than plasma levels.

Acetaldehyde forms stable and unstable adducts with proteins. This can
impair protein function, as evidenced by inhibition of enzyme activity,
impaired histone-DNA binding

Mutagenicity and related end-points

Acetaldehyde is genotoxic in vitro, inducing gene mutations, clastogenic
effects, and sister-chromatid exchanges (SCEs) in mammalian cells in the
absence of exogenous metabolic activation.

There is indirect evidence from in vitro and in vivo studies to suggest
that acetaldehyde can induce protein-DNA and DNA-DNA cross-links.

http://www.inchem.org/documents/ehc/ehc/ehc167.htm

[G-A]

On Wed, 14 Jul 2004 15:30:22 GMT, Ron <can@the.spam> wrote:

>I don't think NE posted anything that claimed ethanol "changes genes";
>only that ethenal can affect gene expression.

But he did. He pasted a piece by some idiot journo saying
exactly this: "Using the latest DNA technology, scientists
in Texas have found that alcohol abuse can alter genes in
the brain". And this: "Most of the altered genes are related
to white matter in the brain called myelin". I hope you'd
agree that "changes" = "alters".

Now, that's not NE's mistake obviously. But if he posts
scientific-sounding snippets here, it would be at least
good idea to make sure they are not completely wrong.

>Does knowing this cure
>alcoholism? Nope. In fact, I don't think it will change anything about
>what I do today, tommorrow, or the day after. I still think it's
>interesting to know, though; and I'm glad people study that kind of
>stuff. Nothing to get bent out of shape about...

Oh but it may change all these 10 years from now! Ten years ago
there was really very little that helped smokers to quit. Now
there is Zyban (bupropion/Wellbutrin) which does absolute
wonders in terms of success rate and remission frequency. And
there are now even good hints of what it might be doing to the
brain. In the same vein are alcohol and Naltrexone and
acamprosate. As we learn how it all works, our chances of
successful "cure" increase. (If you don't know how an engine
works, it's pretty difficult to fix it).

>Meaningless? I don't know about that. One of my favorite expressions
>is "A journey of a thousand miles starts with a single step." Don't
>write stuff off just cuz it ain't the whole enchilada.
>
>I'm thinking about that expression a lot as I begin to paint my house.
>I think I hate painting almost as much as I hate plumbing. Good thing
>I'm not drunk up on a high ladder...

Hey, I have never implied the work was meaningless. (Gosh, I used
to do these things myself). I only said that the results have
nothing to do with what the article claimed and that these
results are of zero immediate practical value because we know
so little about brain yet.

G-A

[G-A]

On Wed, 14 Jul 2004 14:11:51 -0400, NeuroEquipoise@webtv.net (neuro equipoise)
wrote:

>Excerpt 3 - Acetaldehyde/gene mutations

Snip. Jeez, acetaldehyde may do this, and may do that.
May does not mean does. A lot of studies on mutagenicity
of ethanol have been done and the consensus is pretty
unequivocal: ethanol is not a mutagene. Drinking
alcoholic beverages does not cause detectable mutations
in the organisms.

http://archive.food.gov.uk/pdf_files/cotcomcocrep.pdf ,
for example.

It does correlate with a bunch of things but correlation
does not mean causual reltionship.

G-A

[Ron]

On Wed, 14 Jul 2004 19:41:50 -0500, G-A <ga@net> wrote:
> On Wed, 14 Jul 2004 15:30:22 GMT, Ron <can@the.spam> wrote:

>>I don't think NE posted anything that claimed ethanol "changes genes";
>>only that ethenal can affect gene expression.

> But he did. He pasted a piece by some idiot journo saying exactly
> this: "Using the latest DNA technology, scientists in Texas have found
> that alcohol abuse can alter genes in the brain".

Who said that, the journal, or the newswire? Maybe you should direct
your frustration at anyone trying to learn biochem by reading reuters
news feeds. I haven't seen anyone like that around here, myself.

> And this: "Most of the altered genes are related to white matter in
> the brain called myelin". I hope you'd agree that "changes" =
> "alters".

If you want to start being obnoxious, I'll be obnoxious back. I enjoy
that.

> Now, that's not NE's mistake obviously. But if he posts

Bzzt, wrong. She.

> scientific-sounding snippets here, it would be at least
> good idea to make sure they are not completely wrong.

Tell us how you do that.

--
AB5DB9CC