Abstract
In this study, we sought to learn whether adverse events such as chronic restraint stress (CRS), or ‘nurture' in the form of environmental enrichment (EE), could modify depression-like behavior and blood biomarker transcript levels in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a genetic model of depression that aided in the identification of blood transcriptomic markers, which successfully distinguished adolescent and adult subjects with major depressive disorders from their matched no-disorder controls. Here, we followed the effects of CRS and EE in adult male WMIs and their genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that does not show depression-like behavior, by measuring the levels of these transcripts in the blood and hippocampus. In WLIs, increased depression-like behavior and transcriptomic changes were present in response to CRS, but in WMIs no behavioral or additive transcriptomic changes occurred. Environmental enrichment decreased both the inherent depression-like behavior in the WMIs and the behavioral difference between WMIs and WLIs, but did not reverse basal transcript level differences between the strains. The inverse behavioral change induced by CRS and EE in the WLIs did not result in parallel inverse expression changes of the transcriptomic markers, suggesting that these behavioral responses to the environment work via separate molecular pathways. In contrast, ‘trait' transcriptomic markers with expression differences inherent and unchanging between the strains regardless of the environment suggest that in our model, environmental and genetic etiologies of depression work through independent molecular mechanisms.
Highlights
In a 12-month period, major depressive disorder (MDD) affects 6.9% of US individuals[1] and confers the greatest disability among any mental or behavioral disorder worldwide.[2]
EE decreased immobility of both strains, more apparent in the Wistar Kyoto More Immobile (WMI), Wistar Kyoto Less Immobile (WLI) showed a similar effect when probed by a hypothesis testing t-test (Bonferroni post hoc WMI: P o0.01; WLI: t(17) = 2.93, P = 0.01)
In the current study, we identified that chronic restraint stressinduced elevation in depression-like behavior is strain dependent, while environmental enrichment-mediated attenuation of this behavior is independent of genetic background
Summary
In a 12-month period, major depressive disorder (MDD) affects 6.9% of US individuals[1] and confers the greatest disability among any mental or behavioral disorder worldwide.[2]. Genetic variations underlying depression have remained elusive despite large genome-wide association studies[10,11] until recently, when using a very wellcharacterized and homogeneous patient population with severe MDD led to the identification of two candidate sequence variations significantly associated with MDD.[12] Regarding the interaction of the genetic and environmental risk factors, mainly single gene by environment interactions have been explored;[13,14,15,16] but it is not known how the polygenic genetic risk factors interact with the environment to confer risk for MDD. Similar to MDD, WMIs respond to antidepressant treatments,[24] show sex differences in their depression onset and in comorbid anxiety,[25] and display dysfunctions in resting-state hippocampal connectivity.[26,27] The genetically similar, but behaviorally distinct
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
