Early stress produces (long-term) epigenetic changes
Lance
Posted by Jef Akst
[Entry posted at 8th November 2009 06:00 PM GMT]
Scientists have figured out how stress experienced early in life can
cause long-lasting changes in physiology and behavior -- via
epigenetics.
Image: Max-Planck Institute of
Psychiatry, Munich
Specifically, early stress appears to induce epigenetic changes in a
specific regulatory region of the genome, affecting the expression of
a hormone important in controlling mood and cognition into adulthood,
according to a study published online today (November 8) in Nature
Neuroscience.
This is the first study to depict a molecular mechanism by which
"stress early in life can cause effects that remain later in life,"
said epigeneticist Moshe Szyf of McGill University in Montreal. "This
can explain a lot of things that happen to us as humans and our
behavior later in life."
Stress endured early in life can influence the quality of physical and
mental health in adulthood, such as by causing hormonal alterations
associated with mood and cognitive disorders. But until now,
scientists did not understand the mechanism by which early life
experiences can produce such long-lasting effects.
According to a common hypothesis, the environment affects mental
health by causing alterations to the physical properties of the genome
that influence gene expression -- the epigenome. Indeed, research
suggests that DNA methylation, one of the most intensely studied forms
of epigenetics, may explain why maternal care has a long-term
influence on behavior and hormones in rats.
To explore whether DNA methylation is behind the changes associated
with stress experienced early in life, molecular biologists Chris
Murgatroyd and Dietmar Spengler of the Max Planck Institute of
Psychiatry in Germany and colleagues examined the methylation patterns
of mice that were separated from their mothers for three hours a day
for the first ten days of their lives. Specifically, the researchers
looked for differences in the gene that encodes arginine vasopressin
(AVP), a hormone associated with mood and cognitive behaviors. The AVP
receptor is also a promising therapeutic target for stress-related
disorders.
From 6 weeks of age all the way up to 1 year, mice that experienced
early stress -- and showed the predicted behavioral and hormonal
differences -- also displayed significantly lower levels of
methylation in the regulatory region of the Avp gene in the brain.
This hypomethylation was specific to a subset of neurons in the
hypothalamic paraventricular nucleus -- a brain area involved in
regulating hormones linked to stress. These mice also had higher
levels of Avp mRNA, suggesting that lower methylation levels do indeed
affect hormone levels.
"Essentially the genome memorizes that [early life] stress," said
Szyf, who was not involved in the study. "Stress changes methylation,
and that stays the whole life."
The researchers further determined that the decreases in methylation
in stressed mice result from the inactivation of a protein known as
MeCP2, which is involved in the initial recruitment of proteins that
methylate the DNA.
The concept that social states in early life can affect health in
later life is "a completely revolutionary idea," Szyf said. This paper
provides a "detailed" molecular mechanism by which this can occur, and
"gives substance" to this theory.
Understanding the molecular details underlying this phenomenon is
essential to developing potential therapies for mental disorders that
stem from early adverse experiences, Murgatroyd added. "This has given
us new insight in how to possibly develop drugs for [these
illnesses]."
Treatments for reversing the effects of early life stress should begin
as early as possible, Spengler said. Reversing the inactivation of
MeCP2 might be possible, but "once [methylation] is laid down, you
cannot erase [it]," he said. "This is a mark that is very stable."
Treatments given later in life, then, must find ways to ameliorate the
phenotype, such as by blocking AVP receptors in animals with higher
AVP levels, he added.
Source: TheScientist
http://www.the-scientist.com/blog/display/56139/