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<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
Hour="17" Minute="0">17:00</st1:time> <st1:date Month="11" Day="17"
Year="2005">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 Month="12" Day="13"
Year="2002">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 FAMILY="SANSSERIF" PTSIZE="10">----------<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></FONT></BODY></HTML>