http://www.jneurosci.org/content/33/27/11048.abstract
Abstract
Some personality traits, including
novelty seeking, are good predictors of vulnerability to stress-related
mood disorders
in both humans and rodents. While
high-novelty-seeking rats [high responders (HRs)] are vulnerable to the
induction of depressive-like
symptoms by social defeat stress,
low-novelty-seeking rats [low responders (LRs)] are not. Here, we show
that such individual
differences are critically regulated by
hippocampal BDNF. While LR animals exhibited an increase in BDNF levels
following
social defeat, HR individuals did not. This
difference in hippocampal BDNF expression promoted the vulnerability of
HR and
the resilience of LR rats. Indeed, preventing
activation of BDNF signaling by infusing the BDNF scavenger TrkB-Fc into
the
dentate gyrus of the hippocampus of LR rats led
to social defeat-induced social avoidance, whereas its activation in HR
rats
by the TrkB agonist 7,8-dihydroxyflavone
promoted social approach. Along with the changes in BDNF expression
following defeat,
we report in LR animals a downregulation of the
inactive BDNF receptor TrkB.T1, associated with an activation of CREB
through
Akt-mediated signaling, but not MSK1-mediated
signaling. In HR animals, none of these molecules were affected by
social defeat.
Importantly, the BDNF upregulation involved an
epigenetically controlled transcription of bdnf exon VI,
associated with a coherent regulation of relevant epigenetic factors.
Altogether, our data support the importance
of hippocampal BDNF regulation in response to
stressful events. Moreover, we identify a specific and adaptive
regulation of
bdnf exon VI in the hippocampus as a critical regulator of stress resilience, and strengthen the importance of epigenetic factors
in mediating stress-induced adaptive and maladaptive responses in different individuals.
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