Abstract
Background:In the learned helplessness (LH) paradigm, approximately 35% of rats are resilient to inescapable stress.Methods:The roles of brain-derived neurotrophic factor (BDNF) and dendritic spine density in the brain regions of LH (susceptible) and non-LH rats (resilient) were examined. Western blot analysis and Golgi staining were performed.Results:BDNF levels in the medial prefrontal cortex, CA3, and dentate gyrus (DG) were significantly lower in the LH group than in the control and non-LH groups, whereas BDNF levels in the nucleus accumbens (NAc) in the LH group but not the non-LH group were significantly higher than those in the control group. Furthermore, spine density in the prelimbic cortex, CA3, and DG was significantly lower in the LH group than in the control and non-LH groups, although spine density in the NAc was significantly higher in the LH group than in the control and non-LH groups.Conclusions:The results suggest that regional differences in BDNF levels and spine density in rat brain may contribute to resilience to inescapable stress.
Highlights
Humans display wide variability in their responses to psychological stress
The results suggest that regional differences in brain-derived neurotrophic factor (BDNF) levels and spine density in rat brain may contribute to resilience to inescapable stress
Post hoc analyses demonstrated that the BDNF levels in the medial PFC (mPFC) in the learned helplessness (LH) group were significantly lower than those in the control (p < 0.001) and non-LH groups (p < 0.01) and that the BDNF levels in the mPFC were significantly lower in the non-LH group (p < 0.05) than in the control group (Figure 1B)
Summary
Humans display wide variability in their responses to psychological stress. Accumulating evidence suggests that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways (Feder et al, 2009). Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of stress-related mental disorders such as depression, and in the therapeutic mechanism of antidepressants (Nestler et al, 2002; Hashimoto et al, 2004, Duman and Monteggia, 2006; Hashimoto, 2010, 2013; Duman and Li, 2012; Lindholm and Castrén, 2014). Results: BDNF levels in the medial prefrontal cortex, CA3, and dentate gyrus (DG) were significantly lower in the LH group than in the control and non-LH groups, whereas BDNF levels in the nucleus accumbens (NAc) in the LH group but not the non-LH group were significantly higher than those in the control group. Conclusions: The results suggest that regional differences in BDNF levels and spine density in rat brain may contribute to resilience to inescapable stress
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