Gene regulation and depression

Mice subjected to stress caused by the presence of an aggressive intruder, repress the gene that produces a growth factor called brain derived neurotrophic factor (BDNF), reports a paper in the March issue of Nature Neuroscience. This finding suggests a molecular pathway by which stress may cause lasting changes in gene regulation

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*Gene regulation and depression - Nature Neuroscience
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[1] Gene regulation and depression

DOI: 10.1038/nn1659

Mice subjected to stress caused by the presence of an aggressive intruder,
repress the gene that produces a growth factor called brain derived
neurotrophic factor (BDNF), reports a paper in the March issue of Nature
Neuroscience. This finding suggests a molecular pathway by which stress may
cause lasting changes in gene regulation.

Eric Nestler and colleagues have previously reported that such socially
stressed mice show a form of depression that mimics the human condition, and
that treatment with antidepressants can improve their behavior. The team now
uses this model to study gene changes that take place when mice are exposed
to chronic defeat stress and when they are treated with antidepressants.
These changes last for over a month after the social stress ends and are
mediated by an increase in histone methylation - which usually represses
gene expression - at the Bdnf promoter sites, leading to more stable
repression of the gene. Treatment with the antidepressant imipramine
increased histone acetylation - which usually promotes gene expression - by
repressing an enzyme that deacetylates histones, thus reversing the effect
on the Bdnf promoter.

If similar changes occur in humans, which are yet to be demonstrated, this
work may lead to new therapeutic targets for stress-induced depression.

Author contact:
Eric Nestler (University of Texas Southwestern Medical Center, TX, USA)
Tel: +1 214 648 1111; E-mail: [email protected]

Additional contact for comment on paper:
Steven Hyman (Harvard Medical School, MA, USA)
Tel: +1 617 496 5100; E-mail: [email protected]

Other papers from Nature Neuroscience to be published online at the same
time and with the same embargo:

[2] Selective enhancement of associative learning by microstimulation of the
anterior caudate DOI: 10.1038/nn1662

[3] Brain activity before an event predicts later recollection DOI: 10.1038/nn1663

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[6] Kinetic development of crystallization fronts in complex plasmas
DOI: 10.1038/nphys242

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GEOGRAPHICAL LISTING OF AUTHORS

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AUSTRALIA
Victoria: 12, 1

BELGIUM
Ghent: 17

CANADA
Alberta: 11

FRANCE
Orleans: 6
Paris: 14

GERMANY
Berlin: 5, 17
Cologne: 17
Dortmund: 17
Garching: 5, 6
Giessen: 14
Leipzig: 5

IRELAND
Dublin: 15

ISRAEL
Jerusalem: 12

ITALY
Catanzova: 10

NORWAY
Tromso: 6

RUSSIA
Chernogolovka: 8

SWEDEN
Umea: 15

SWITZERLAND
Basel: 4

THE NETHERANDS
Amsterdam: 16
Nijmegen: 8, 17
Rotterdam: 12

TURKEY
Istanbul: 17

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Bath: 15
Belfast: 15
Birmingham: 15
Lancaster: 8
Leeds: 17
London: 3
Manchester: 8

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California
Irvine: 3
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Los Angeles: 14
Stanford: 13
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New Haven: 17, 19
Dallas
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