Variable impact of chronic stress on spatial learning and memory in BXD mice

Abstract

The effects of chronic stress on learning are highly variable across individuals. This variability stems from gene-environment interactions. However, the mechanisms by which stress affects genetic predictors of learning are unclear. Thus, we aim to determine whether the genetic pathways that predict spatial memory performance are altered by previous exposure to chronic stress. Sixty-two BXD recombinant inbred strains of mice, as well as parent strains C57BL/6J and DBA/2J, were randomly assigned as behavioral control or to a chronic variable stress paradigm and then underwent behavioral testing to assess spatial memory and learning performance using the Morris water maze. Quantitative trait loci (QTL) mapping was completed for average escape latency times for both control and stress animals. Loci on chromosomes 5 and 10 were found in both control and stress environmental populations; eight additional loci were found to be unique to either the control or stress environment. In sum, results indicate that certain genetic loci predict spatial memory performance regardless of prior stress exposure, while exposure to stress also reveals unique genetic predictors of training during the memory task. Thus, we find that genetic predictors contributing to spatial learning and memory are susceptible to the presence of chronic stress.

Genetic divergence in the transcriptional engram of chronic alcohol abuse: A laser-capture RNA-seq study of the mouse mesocorticolimbic system

“…Indeed, McCool and colleagues found a robust increase in alcohol self-administration in both B6 and D2 following multiple cycles of CIE using an umami-fading procedure that produces high levels of baseline alcohol consumption in both strains (McCool & Chappell, 2015). B6 and D2 also show profound differences in the behavioral and physiological response to acute (Belzung, El Hage, Moindrot, & Griebel, 2001; Jacobson & Cryan, 2007; Jones, Sarrieau, Reed, Azar, & Mormède, 1998; Millstein & Holmes, 2007) and chronic (Mozhui et al, 2010; Pleil et al, 2012; Pothion, Bizot, Trovero, & Belzung, 2004; Shea et al., 2015) stress. This differential response to stress could account for some of the transcriptional differences between strains following CIE. Our results, combined with recent studies, provide evidence that the D2 strain is a unique and genetically distinct model for investigating the contribution of stress and alcohol interactions to addiction and alcohol-use disorders.…”

Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

“…Subsequently, each diet group was subdivided into control or stress ( n = 10/group) to investigate whether prolonged exposure to endogenous vs. exogenous ketones could mitigate challenge-induced detriments on behavioral performance. The stress paradigm adopted was chosen according the published studies on chronic variable stress on rodents (Herman et al, 2008; Jankord and Herman, 2008; Shea et al, 2015) and consisted of once-daily exposure to randomly assigned stressors. Restraint stress was performed by inserting the animals into a custom made well-ventilated, flat bottom clear plastic rodent restrainer for 1 h. Cold exposure consisted of placing cages (with no food, bedding or water) in a cold room at 4°C for 30 min.…”

Distinct genetic signatures of cortical and subcortical regions associated with human memory

“…For the corresponding negatively correlated genes, nine out of ten had weak evidence for their role in memory ( Table 3). These included ribosomal genes RPS5 and RPS13 which were differentially expressed in Alzheimer's Disease models 124,125 , and RPS16 and RPS25 in long term memory 126,127 . Table 4.…”