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<DIV><SPAN class=452192214-19112005>I recently ran across a biotech company that
is working on</SPAN></DIV>
<DIV><SPAN class=452192214-19112005>technology to turn on any one of the
thousands of enzymes</SPAN></DIV>
<DIV><SPAN class=452192214-19112005>produced by the body.</SPAN></DIV>
<DIV><SPAN class=452192214-19112005></SPAN> </DIV>
<DIV><SPAN class=452192214-19112005>Biotech in general is very involved with
proteins, which the</SPAN></DIV>
<DIV><SPAN class=452192214-19112005>body also creates in the
thousands.</SPAN></DIV>
<DIV><SPAN class=452192214-19112005></SPAN> </DIV>
<DIV><SPAN class=452192214-19112005>Perhaps you should be looking at the brains
in your thorax</SPAN></DIV>
<DIV><SPAN class=452192214-19112005>rather than the brains in your cranium
:-)</SPAN></DIV>
<DIV><SPAN class=452192214-19112005></SPAN> </DIV>
<DIV><SPAN class=452192214-19112005>Steve Hovland</SPAN></DIV>
<DIV><SPAN class=452192214-19112005></SPAN> </DIV>
<BLOCKQUOTE dir=ltr style="MARGIN-RIGHT: 0px">
<DIV class=OutlookMessageHeader dir=ltr align=left><FONT
face=Tahoma>-----Original Message-----<BR><B>From:</B>
paleopsych-bounces@paleopsych.org
[mailto:paleopsych-bounces@paleopsych.org]<B>On Behalf Of
</B>HowlBloom@aol.com<BR><B>Sent:</B> Friday, November 18, 2005 10:19
PM<BR><B>To:</B> paleopsych@paleopsych.org<BR><B>Cc:</B>
planetbloom@hotmail.com; bdyed@earthlink.net<BR><B>Subject:</B> [Paleopsych]
kicking fear around with proteins<BR><BR></FONT></DIV><FONT id=role_document
face=Arial size=2>
<DIV>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt">Put
the following two articles together and you get the following conclusion:<SPAN
style="mso-spacerun: yes"> </SPAN></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"></SPAN> </P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt">The
protein stathmin kicks fear<SPAN style="mso-spacerun: yes"> </SPAN>into
high gear and the protein gastrin stomps the pedal of fear’s brakes.
</SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"></SPAN> </P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt">Gastrin
is a protein from the intestines, a protein involved in having a good
meal.<SPAN style="mso-spacerun: yes"> </SPAN>So does being well fed
should make you fearless?<SPAN style="mso-spacerun: yes"> </SPAN>The
folks who made up our clichés may have been more accurate than they knew when
they said that people who are fearless “have guts.”<o:p></o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><o:p> </o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt">By
the way, I’ve been looking for the stress-handling system in the brain for the
last decade.<SPAN style="mso-spacerun: yes"> </SPAN>It looks as if the
stathmin and gastrin system may be a part of it.<SPAN
style="mso-spacerun: yes"> </SPAN></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"></SPAN> </P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt">When
I came down with Chronic Fatigue Syndrome in 1988 and my stress handling
system lost its inhibitory abilities and ramped up my stress sensitivity
beyond all imagining, was I overloaded with stathmin and stripped of
gastrin? Howard<o:p></o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt">________<o:p></o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=3>Retrieved <SPAN
style="mso-no-proof: yes">November 18, 2005</SPAN>, from the World Wide
Web<SPAN style="mso-spacerun: yes">
</SPAN>http://www.newscientist.com/article.ns?id=dn8337 </FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=3>Gene turn-off
makes meek mice fearless<SPAN style="mso-spacerun: yes"> </SPAN>*
<st1:time Minute="0" Hour="17">17:00</st1:time> <st1:date Year="2005" Day="17"
Month="11">17 November 2005</st1:date> * NewScientist.com news service
Deactivating a specific gene transforms meek mice into daredevils, researchers
have found. The team believe the research might one day enable people
suffering from fear – in the form of phobias or anxiety disorders, for example
– to be clinically treated.</FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=3><SPAN
style="mso-spacerun: yes"> </SPAN>The research found that mice lacking
an active gene for the protein stathmin are not only more courageous, but are
also slower to learn fear responses to pain-associated stimuli, says
geneticist Gleb Shumyatsky, at Rutgers University in New Jersey, US.<SPAN
style="mso-spacerun: yes"> </SPAN>In the experiments, the
stathmin-lacking mice wandered out into the centre of an open box, in defiance
of the normal mouse instinct to hide along the box’s walls to avoid potential
predators.<SPAN style="mso-spacerun: yes"> </SPAN>And to test learned
fear, the mice were exposed to a loud sound followed by a brief electric shock
from the floor below them. A day later, normal mice froze when the sound was
played again. Stathmin-lacking mice barely reacted to the sound at all. Neural
responses<SPAN style="mso-spacerun: yes"> </SPAN>In both mice and
humans, the amygdala area of the brain serves as the control centre of basic
fear impulses. Stathmin is found almost exclusively in this and related brain
areas.<SPAN style="mso-spacerun: yes"> </SPAN>The protein is known to
destabilise microtubule structures that help maintain the connections between
neurons. This allows the neurons to make new connections, allowing the animal
to learn and process fear experiences, Shumyatsky says. Without it, the neural
responses are stilted.<SPAN style="mso-spacerun: yes"> </SPAN>The lack
of the protein does not appear to affect other learning experiences, as both
sets of mice were able to memorise the paths out of mazes equally well. “This
is a good sign for an eventual clinical application that could let people deal
with their fears in an entirely different way,” Shumyatsky says.<SPAN
style="mso-spacerun: yes"> </SPAN>In 2002, Shumyatsky and colleagues
published a study on a similar gene encoding for a protein called GRP. But
this protein seems only to be associated with learned fear, and would
therefore only have clinical implications for conditions such as
post-traumatic stress disorder.<SPAN style="mso-spacerun: yes">
</SPAN><B style="mso-bidi-font-weight: normal">Stathmin,</B> on the other
hand, seems to affect both learned and innate fear, which could lead to
treatments for a much broader range of phobias and anxiety disorders,
Shumyatsky says.<SPAN style="mso-spacerun: yes"> </SPAN>Journal
reference: Cell (DOI: 10.1016/j.cell.2005.08.038) Printable version Email to a
friend RSS Feed Cover of latest issue of New </FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt"><o:p> </o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><SPAN
style="FONT-SIZE: 12pt; LETTER-SPACING: -0.15pt; mso-bidi-font-size: 10.0pt">_________<o:p></o:p></SPAN></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=3>Site:<SPAN
style="mso-spacerun: yes"> </SPAN>ScienceDaily Magazine Page URL:
http://www.sciencedaily.com/releases/2002/12/021213062425.htm<SPAN
style="mso-spacerun: yes"> </SPAN>Original Source: Howard Hughes Medical
Institute Date Posted: <st1:date Year="2002" Day="13"
Month="12">12/13/2002</st1:date> Researchers Discover Gene That Controls
Ability To Learn Fear <B>Researchers have discovered the first genetic
component of a biochemical pathway in the brain that governs the indelible
imprinting of fear-related experiences in memory.</B> <B><SPAN
style="mso-spacerun: yes"> </SPAN>The gene</B> identified by researchers
at the Howard Hughes Medical Institute at
<st1:place><st1:PlaceName>Columbia</st1:PlaceName>
<st1:PlaceType>University</st1:PlaceType></st1:place> <B>encodes a protein
that inhibits the action of the fear-learning circuitry in the brain.</B>
Understanding how this protein quells fear may lead to the design of new drugs
to treat depression, panic and generalized anxiety disorders.<SPAN
style="mso-spacerun: yes"> </SPAN>The findings were reported in the
December 13, 2002 issue of the journal Cell, by a research team that included
Howard Hughes Medical Institute (HHMI) investigators Eric Kandel at Columbia
University and Catherine Dulac at Harvard University. Lead author of the paper
was Gleb Shumyatsky, a postdoctoral fellow in Kandel's laboratory at
<st1:place><st1:PlaceName>Columbia</st1:PlaceName>
<st1:PlaceType>University</st1:PlaceType></st1:place>. Other members of the
research team are at the National Institutes of Health and
<st1:place><st1:PlaceName>Harvard</st1:PlaceName>
<st1:PlaceName>Medical</st1:PlaceName>
<st1:PlaceType>School</st1:PlaceType></st1:place>.<SPAN
style="mso-spacerun: yes"> </SPAN>According to Kandel, earlier studies
indicated that a specific signaling pathway controls <B>fear-related
learning</B>, which <B>takes place in</B> a region of the brain called <B>the
amygdala.</B> "Given these preliminary analyses, we wanted to take a more
systematic approach to obtain a genetic perspective on learned fear," said
Kandel.<SPAN style="mso-spacerun: yes"> </SPAN>One of the keys to doing
these genetic analyses, Kandel said, was the development of a technique for
isolating and comparing the genes of individual cells, which was developed at
<st1:City><st1:place>Columbia</st1:place></st1:City> by Dulac with HHMI
investigator Richard Axel. Shumyatsky applied that technique, called
differential screening of single-cell cDNA libraries, to mouse cells to
compare the genetic activity of cells from a region of the amygdala called the
lateral nucleus, with cells from another region of the brain that is not known
to be involved in learned fear. The comparison revealed two candidate genes
for fear-related learning that are highly expressed in the amygdala.<SPAN
style="mso-spacerun: yes"> </SPAN>The researchers decided to focus
further study on <B>one of the genes, Grp, which encodes a short protein
called gastrin-releasing peptide (GRP),</B> because they found that <B>this
protein has an unusual distribution in the brain and is known to serve as a
neurotransmitter. </B>Shumyatsky's analysis revealed that <B>the Grp gene was
highly enriched in the lateral nucleus, and in other regions of the brain that
feed auditory inputs into the amygdala.</B><SPAN
style="mso-spacerun: yes"> </SPAN><B>"Gleb's finding that this gene was
active not only in the lateral nucleus but also in a number of regions that
projected into the lateral nucleus was interesting because it suggested that a
whole circuit was involved,"</B> said Kandel. Shumyatsky next showed that
<B>GRP is expressed by excitatory principal neurons and that its receptor,
GRPR, is expressed by inhibitory interneurons.</B> The researchers then
undertook collaborative studies with co-author Vadim Bolshakov at
<st1:place><st1:PlaceName>Harvard</st1:PlaceName>
<st1:PlaceName>Medical</st1:PlaceName>
<st1:PlaceType>School</st1:PlaceType></st1:place> to characterize cells in the
amygdala that expressed receptors for GRP. Those studies in mouse brain slices
revealed that <B>GRP acts in the amygdala by exciting a population of
inhibitory interneurons in the lateral nucleus that provide feedback and
inhibit the principal neurons.<o:p></o:p></B></FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><FONT size=3><SPAN
style="mso-spacerun: yes"> </SPAN>The researchers next explored whether
eliminating GRP's activity could affect the ability to learn fear by studying
a strain of <B>knockout mice that lacked the receptor for GRP in the
brain</B>.<SPAN style="mso-spacerun: yes"> </SPAN>In behavioral
experiments, they first trained both the knockout mice and normal mice to
associate an initially neutral tone with a subsequent unpleasant electric
shock. As a result of the training, the mouse learns that the neutral tone now
predicts danger. After the training, the researchers compared the degree to
which the two strains of mice showed fear when exposed to the same tone alone
-- by measuring the duration of a characteristic freezing response that the
animals exhibit when fearful.<SPAN style="mso-spacerun: yes">
</SPAN>"When we compared the mouse strains, <B>we saw a powerful enhancement
of learned fear in the knockout mice,"</B> said Kandel. Also, he said, the
knockout mice showed an enhancement in the learning-related cellular process
known as long-term potentiation.<SPAN style="mso-spacerun: yes">
</SPAN>"It is interesting that we saw no other disturbances in these mice," he
said. "They showed no increased pain sensitivity; nor did they exhibit
increased instinctive fear in other behavioral studies. So, their defect
seemed to be quite specific for the learned aspect of fear," he said. Tests of
instinctive fear included comparing how both normal and knockout mice behaved
in mazes that exposed them to anxiety-provoking environments such as open or
lighted areas.<SPAN style="mso-spacerun: yes"> </SPAN>"These findings
reveal a biological basis for what had only been previously inferred from
psychological studies -- that instinctive fear, chronic anxiety, is different
from acquired fear," said Kandel.<SPAN style="mso-spacerun: yes">
</SPAN>In additional behavioral studies, the researchers found that the normal
and knockout mice did not differ in spatial learning abilities involving the
hippocampus, but not the amygdala, thus genetically demonstrating that these
two anatomical structures are different in their function.<SPAN
style="mso-spacerun: yes"> </SPAN>According to Kandel, further
understanding of the fear-learning pathway could have important implications
for treating anxiety disorders. "Since GRP acts to dampen fear, it might be
possible in principle to develop drugs that activate the peptide, representing
a completely new approach to treating anxiety," he said. However, he
emphasized, the discovery of the action of the Grp gene is only the beginning
of a long research effort to reveal the other genes in the fear-learning
pathway.<SPAN style="mso-spacerun: yes"> </SPAN>More broadly, said
Kandel, the fear-learning pathway might provide an invaluable animal model for
a range of mental illnesses. "Although one would ultimately like to develop
mouse models for various mental illnesses such as schizophrenia and
depression, this is very hard to do because we know very little about the
biological foundations of most forms of mental illness," he said. "However, we
do know something about the neuroanatomical substrates of anxiety states,
including both chronic fear and acute fear. We know they are centered in the
amygdala.<SPAN style="mso-spacerun: yes"> </SPAN>"And while I don't want
to overstate the case, in studies of fear learning we could well have an
excellent beginning for animal models of a severe mental illness. We already
knew quite a lot about the neural pathways in the brain that are involved in
fear learning. And now, we have a way to understand the genetic and
biochemical mechanisms underlying those pathways."<SPAN
style="mso-spacerun: yes"> </SPAN>Editor's Note: The original news
release can be found here.<SPAN style="mso-spacerun: yes"> </SPAN>Note:
This story has been adapted from a news release issued for journalists and
other members of the public. If you wish to quote from any part of this story,
please credit Howard Hughes Medical Institute as the original source.<SPAN
style="mso-spacerun: yes"> </SPAN></FONT></P>
<P class=MsoNormal style="MARGIN: 0in 0in 0pt"><o:p><FONT
size=3> </FONT></o:p></P></DIV>
<DIV><FONT size=3></FONT> </DIV>
<DIV><FONT lang=0 size=3 PTSIZE="10" FAMILY="SANSSERIF">----------<BR>Howard
Bloom<BR>Author of The Lucifer Principle: A Scientific Expedition Into the
Forces of History and Global Brain: The Evolution of Mass Mind From The Big
Bang to the 21st Century<BR>Recent Visiting Scholar-Graduate Psychology
Department, New York University; Core Faculty Member, The Graduate
Institute<BR>www.howardbloom.net<BR>www.bigbangtango.net<BR>Founder:
International Paleopsychology Project; founding board member: Epic of
Evolution Society; founding board member, The Darwin Project; founder: The Big
Bang Tango Media Lab; member: New York Academy of Sciences, American
Association for the Advancement of Science, American Psychological Society,
Academy of Political Science, Human Behavior and Evolution Society,
International Society for Human Ethology; advisory board member: Institute for
Accelerating Change ; executive editor -- New Paradigm book series.<BR>For
information on The International Paleopsychology Project, see:
www.paleopsych.org<BR>for two chapters from <BR>The Lucifer Principle: A
Scientific Expedition Into the Forces of History, see
www.howardbloom.net/lucifer<BR>For information on Global Brain: The Evolution
of Mass Mind from the Big Bang to the 21st Century, see
www.howardbloom.net<BR></FONT></DIV></BLOCKQUOTE></FONT></BODY></HTML>