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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Tuesday, July 23, 2013
A mechanism of why novelty seeking individuals are more vulnerable to social defeat stress.
Duclot and Kabbaj offer an interesting result that suggests at least part of the reason for why individuals more likely to seek novelty (whether humans or mice) are also more vulnerable to social defeat stress. They do not demonstrate the stress induced increase in levels of a brain growth factor (brain derived neurotrophic factor, or BNDF), that is observed in low novelty seeking individuals. BDNF regulation after stress has been suggested as an important mediator of vulnerability and resilience. Higher BDNF levels in the hippocampus - which can be caused by classic antidepressants - promote resilience to a chronic mild stress. Here is the abstract, with technical details:
Posted by Deric Bownds at 9:55 AM
Blog Categories: fear/anxiety/stress
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This is really interesting. I wonder what the systemic/population adaptive value is for novelty seekers to be prone to social defeat stress? And for low novelty seekers to be protected against social defeat stress? One might propose a theory whereby the novelty seekers are motivated to engage in some level of adaptive social change.ReplyDelete
Hmmmm... and the stress sensitivity is a feedback mechanism to enhance probability that a (socially) novel behavior is congenial to conspecifics?? We're kind of getting out on a limb here.ReplyDelete
Actually I'm thinking more along the lines of Richerson and Boyd's dual inheritance theory whereby human culture evolves along side human biology. Sensitivity to social defeat could motivate cultural innovations because the status quo would be both unappealing to novelty seekers (by definition) and very stressful (via the absent hippocampal BDNF). Such novelty seekers may then be intrinsically motivated toward cultural innovation and extrinsically motivated by social defeat.ReplyDelete
Richerson and Boyd propose that prestige and imitation are the primary vectors of cultural inheritance but they also discuss a much more unusual vector that introduces variation and innovation because it's carriers are intrinsically motivated to reject the status quo. It strikes me that social defeat stress may play a role in that dynamic by inspiring innovation (although it would ostensibly sometimes result in learned helplessness as well). I know I've experienced both!
Apologies for straying pretty far beyond the domain of this blog. I'll have to work this out further to understand if its completely coherent and not just a little bit circular. It very well could be the case that the stress proneness simply accompanies high novelty seeking (and need for cognition) and that the low stress proneness simply accompanies low novelty seeking (and the need for cognitive closure) as byproducts of those primary interests in novelty or sameness.