Sex-Specific Behavioral Response to Early Adolescent Stress in the Genetically More Stress-Reactive Wistar Kyoto More Immobile, and Its Nearly Isogenic Wistar Kyoto Less Immobile Control Strain

Kim, Sarah; Gacek, Stephanie A.; Mocchi, Madaline M.; Redei, Eva E.

doi:10.3389/fnbeh.2021.779036

Cited by 3 publications

(1 citation statement)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stress during adolescence is thought to be a major contributor to psychopathology in adulthood [ 161 ]. In both WMI and WLI rats, a very mild single stress during early adolescence significantly decreases anxiety-like behavior, measured in the OFT, and increases social interaction and recognition in adult males compared to controls [ 162 ]. In contrast, no significant effects of early adolescent stress are observed in adult females of either strain in these behaviors.…”

Section: Selective Breeding: Wmi and Wli Substrainsmentioning

confidence: 99%

The Wistar Kyoto Rat: A Model of Depression Traits

Redei

Udell

Solberg‐Woods

et al. 2023

Self Cite

View full text Add to dashboard Cite

There is an ongoing debate about the value of animal research in psychiatry with valid lines of reasoning stating the limits of individual animal models compared to human psychiatric illnesses. Human depression is not a homogenous disorder; therefore, one cannot expect a single animal model to reflect depression heterogeneity. This limited review presents arguments that the Wistar Kyoto (WKY) rats show intrinsic depression traits. The phenotypes of WKY do not completely mirror those of human depression but clearly indicate characteristics that are common with it. WKYs present despair-like behavior, passive coping with stress, comorbid anxiety, and enhanced drug use compared to other routinely used inbred or outbred strains of rats. The commonly used tests identifying these phenotypes reflect exploratory, escape-oriented, and withdrawal-like behaviors. The WKYs consistently choose withdrawal or avoidance in novel environments and freezing behaviors in response to a challenge in these tests. The physiological response to a stressful environment is exaggerated in WKYs. Selective breeding generated two WKY substrains that are nearly isogenic but show clear behavioral differences, including that of depression-like behavior. WKY and its substrains may compare characteristics of subgroups of depressed individuals with social withdrawal, low energy, weight loss, sleep disturbances, and specific cognitive dysfunction. The genomes of the WKY and WKY substrains contain variations that impact the function of many genes identified in recent human genetic studies of depression. Thus, these strains of rats share characteristics of human depression at both phenotypic and genetic levels, making them a model of depression traits.

show abstract

Section: Selective Breeding: Wmi and Wli Substrainsmentioning

confidence: 99%

The Wistar Kyoto Rat: A Model of Depression Traits

Redei

Udell

Solberg‐Woods

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

Limited WKY chromosomal regions confer increases in anxiety and fear memory in a F344 congenic rat strain

Ji,

Pashankar,

Harter

et al. 2024

Physiological Genomics

View full text Add to dashboard Cite

This study investigated the interaction between genetic differences in stress reactivity/coping and environmental challenge, such as acute stress during adolescence on adult contextual fear memory and anxiety-like behaviors. Fischer 344 (F344) and the inbred F344;WKY-Stresp3/Eer congenic strain (congenic), in which chromosomal regions from the Wistar Kyoto (WKY) strain were introgressed into the F344 background, were exposed to a modified Forced Swim Test (FST) during adolescence while controls were undisturbed. In adulthood, fear learning and memory, assessed by Contextual Fear Conditioning (CFC), were significantly greater in congenic animals compared to F344s, and stress during adolescence increased them even further in males of both strains. Anxiety-like behavior, measured by the Open Field Test (OFT), were also greater in congenics than F344s, and stress during adolescence increased it further in both strains of adult males. Whole genome sequencing of the F344;WKY-Stresp3/Eer strain revealed an enrichment of WKY genotypes in Chromosomes 9,14 and 15. An example of functional WKY sequence variations in the congenic strain, Cannabinoid Receptor Interacting Protein 1 (Cnrip1) had a Cnrip1 transcript isoform that lacked two exons. Although the original hypothesis that the genetic predisposition to increased anxiety of the WKY donor strain would exaggerate fear memory relative to the background strain was confirmed, the consequences of adolescent stress were strain independent but sex dependent in adulthood. Molecular genomic approaches combined with genetic mapping of WKY sequence variations in Chrs 9,14, and 15 could aid in finding quantitative trait genes contributing to the variation in fear memory.

show abstract

Imbalance in Sirt1 Alternative Splicing in Response to Chronic Stress during the Adolescence Period in Female Mice

Shlomi

Toledano

Nitzan

et al. 2022

IJMS

View full text Add to dashboard Cite

Stressful unpredictable life events have been implicated in numerous diseases. It is now becoming clear that some life periods are more vulnerable than others. As adolescence is a sensitive period in brain development, the long-term effects of stress during this period could be significant. We investigated the long-term effects of exposure to unpredictable chronic mild stress in adolescent mice on alternative splicing of Sirtuin 1. One-month-old mice were exposed to 4 weeks of UCMS and examined for anxiety and cognition at the age of 2, 4 and 6 months. We found a rise in anxious behavior immediately after the exposure to stress. Notably, there was a long-term impairment of performance in cognitive tasks and an imbalance in Sirtuin 1 and TrkB receptor alternative splicing in the stress-exposed mice compared with controls. To conclude, our results show that exposure to unpredictable chronic mild stress during adolescence affects cognition in adulthood. Understanding pathways affiliated with stress may help minimize the long-term emotional effects of an unpredictable, stressful event.

show abstract

Sex-Specific Behavioral Response to Early Adolescent Stress in the Genetically More Stress-Reactive Wistar Kyoto More Immobile, and Its Nearly Isogenic Wistar Kyoto Less Immobile Control Strain

Cited by 3 publications

References 69 publications

The Wistar Kyoto Rat: A Model of Depression Traits

The Wistar Kyoto Rat: A Model of Depression Traits

Limited WKY chromosomal regions confer increases in anxiety and fear memory in a F344 congenic rat strain

Imbalance in Sirt1 Alternative Splicing in Response to Chronic Stress during the Adolescence Period in Female Mice

Contact Info

Product

Resources

About