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ScienceDaily (Aug. 12, 2012) Major depression
or chronic stress can cause the loss of brain volume,
a condition that contributes to both emotional and
cognitive impairment. Now a team of researchers led
by Yale scientists has discovered one reason why
this occurs -- a single genetic switch that triggers
loss of brain connections in humans and depression
in animal models.
The findings, reported in the Aug. 12
issue of the journal Nature Medicine,
show that the genetic switch known
as a transcription factor represses
the expression of several genes that
are necessary for the formation of
synaptic connections between brain
cells, which in turn could contribute
to loss of brain mass in the prefrontal
cortex.
"We wanted to test the idea that
stress causes a loss of brain
synapses in humans," said senior
author Ronald Duman, the Elizabeth
Mears and House Jameson
Professor of Psychiatry and
professor of neurobiology and of
pharmacology. "We show that
circuits normally involved in emotion,
as well as cognition, are disrupted
when this single transcription factor
is activated."
The research team analyzed tissue
of depressed and non-depressed
patients donated from a brain bank
and looked for different patterns of
gene activation. The brains of
patients who had been depressed
exhibited lower levels of expression
in genes that are required for the
function and structure of brain
synapses. Lead author and
postdoctoral researcher H.J. Kang discovered that at least five
of these genes could be regulated by a single transcription
factor called GATA1. When the transcription factor was
activated, rodents exhibited depressive-like symptoms,
suggesting GATA1 plays a role not only in the loss of
connections between neurons but also in symptoms of
depression.
Duman theorizes that genetic variations in GATA1 may one
day help identify people at high risk for major depression or
sensitivity to stress.
"We hope that by enhancing synaptic connections, either with
novel medications or behavioral therapy, we can develop more
effective antidepressant therapies," Duman said.
The study was funded by the National Institutes of Health and
the Connecticut Department of Mental Health and Addiction
Services.
Other Yale authors of the paper are Bhavya Voleti, Pawel
Licznerski, Ashley Lepack, and Mounira Banasr.
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Story Source:
The above story is reprinted from materials provided by
Yale University.
Note: Materials may be edited for content and length. For
further information, please contact the source cited above.
Journal Reference:
1. Hyo Jung Kang, Bhavya Voleti, Tibor Hajszan, Grazyna
Rajkowska, Craig A Stockmeier, Pawel Licznerski, Ashley
Lepack, Mahesh S Majik, Lak Shin Jeong, Mounira Banasr,
Expression of a single gene dramatically decreases
synaptic connections between brain cells. Yale
scientists believe this may explain why people
suffering from chronic stress and depression suffer
loss of brain volume (Credit: Courtesy Yale
University)
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APA
MLA
Hyeon Son, Ronald S Duman. Decreased expression of
synapse-related genes and loss of synapses in major
depressive disorder. Nature Medicine, 2012; DOI:
10.1038/nm.2886
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Yale University (2012, August 12). How stress
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ScienceDaily. Retrieved August 13, 2012, from
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utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fmind_brain+%28ScienceDaily%3A+Mind+%26+Brain+News%29
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