Strain Differences in Responsiveness to Repeated Restraint Stress Affect Remote Contextual Fear Memory and Blood Transcriptomics

Jung, Soo Yeon; Meckes, Jeanie K.; Schipma, Matthew J.; Lim, Patrick H.; Jenz, Sophia T; Przybyl, K.J.; Wert, Stephanie L.; Kim, Sarah; Luo, Wendy; Gacek, Stephanie A.; Jankord, Ryan; Hatcher-Solis, Candice; Redei, Eva E.

doi:10.1016/j.neuroscience.2020.07.052

Cited by 7 publications

(6 citation statements)

References 55 publications

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“…In response to chronic stress, KO rats showed the expected increases in thigmotaxis in the OFT as well as hyponeophagia and significant decreases in exploratory activity in the NSF. WT rats, on the other hand, displayed only minimal differences in these measures after stress exposure, in contrast to findings after chronic restraint stress in WKYs ( Jung et al, 2020 ). We also found that immobility in the FST increased in stress-exposed KO rats from Day 1 to Day 2 of the test, with minimal changes between days in stress-exposed WT rats.…”

Section: Discussioncontrasting

confidence: 55%

Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3

Szalanczy,

Fitzpatrick,

Beeson

et al. 2024

Front. Genet.

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We previously identified Keratinocyte-associated protein 3, Krtcap3, as a novel adiposity gene, but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection between Krtcap3, adiposity, and stress, we exposed wild-type (WT) and Krtcap3 knock-out (KO) rats to chronic stress then measured adiposity and behavioral outcomes. We found that KO rats displayed lower basal stress than WT rats under control conditions and exhibited metabolic and behavioral responses to chronic stress exposure. Specifically, stress-exposed KO rats gained more weight, consumed more food when socially isolated, and displayed more anxiety-like behaviors relative to control KO rats. Meanwhile, there were minimal differences between control and stressed WT rats. At study conclusion stress-exposed KO rats had increased corticosterone (CORT) relative to control KO rats with no differences between WT rats. In addition, KO rats, independent of prior stress exposure, had an increased CORT response to removal of their cage-mate (psychosocial stress), which was only seen in WT rats when exposed to chronic stress. Finally, we found differences in expression of the glucocorticoid receptor, Nr3c1, in the pituitary and colon between control and stress-exposed KO rats that were not present in WT rats. These data support that Krtcap3 expression affects stress response, potentially via interactions with Nr3c1, with downstream effects on adiposity and behavior. Future work is necessary to more thoroughly understand the role of Krtcap3 in the stress response.

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Section: Discussioncontrasting

confidence: 55%

Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3

Szalanczy,

Fitzpatrick,

Beeson

et al. 2024

Front. Genet.

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“…However, chronic restraint stress still generates elevations in plasma CORT levels that are similar in WKY, Fisher 344 (F344), Brown Norway, and Lewis male rats [ 94 ]. The same stress paradigm affects body weight gain less in WKY than in F344 males and generates blood transcriptomic differences between the strains in control and chronic stress conditions [ 109 ]. Overlapping differentially expressed genes (DEGs) between control and chronic stress in the blood of F344 and WKY suggest a convergence of stress-related molecular mechanisms independent of stress reactivity.…”

Section: Physiological Phenotypesmentioning

confidence: 99%

“…In contrast, DEGs unique to the F344 and the WKY stress responses are divergent in their functionality and networks, beyond that of strain differences in their non-stressed state. Most F344 stress response DEGs overlap with those of WKYs, showing only reduced expressions [ 109 ]. In contrast, integrin signaling and the Fc receptor-mediated phagocytosis in macrophages and monocytes are the two canonical pathways characterizing the DEGs unique to WKYs [ 109 ].…”

Section: Physiological Phenotypesmentioning

confidence: 99%

“…Most F344 stress response DEGs overlap with those of WKYs, showing only reduced expressions [ 109 ]. In contrast, integrin signaling and the Fc receptor-mediated phagocytosis in macrophages and monocytes are the two canonical pathways characterizing the DEGs unique to WKYs [ 109 ]. Both are involved in the removal of pathogens as part of innate and adaptive immunity, and the clearance of apoptotic cells that are generated during development and cell turnover in tissues [ 110 ].…”

Section: Physiological Phenotypesmentioning

confidence: 99%

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The Wistar Kyoto Rat: A Model of Depression Traits

Redei

Udell

Solberg‐Woods

et al. 2023

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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.

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“…Less surprisingly, variability across strains is also prevalent across myriad phenotypes. Jung and colleagues discovered that Fisher 344 and Wistar-Kyoto rats differ in their reactivity to recent and reinstated fear memories, and showed overlapping and divergent blood transcriptome profiles, with strain-specific differentially expressed genes exhibiting different functional enrichments and coexpression (Jung et al, 2020). Jin et al (2017) discovered that citalopram reduces immobility time in the forced swim and tail suspension tests in DBA/2J mice but not C57BL/6J mice, with fluoxetine showing opposite results.…”

Section: Sensitivity Of Results In Animal Research: Generalizability ...mentioning

confidence: 99%

Questionable Research Practices, Low Statistical Power, and Other Obstacles to Replicability: Why Preclinical Neuroscience Research Would Benefit from Registered Reports

Ellis

2022

eNeuro

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Replicability, the degree to which a previous scientific finding can be repeated in a distinct set of data, has been considered an integral component of institutionalized scientific practice since its inception several hundred years ago. In the past decade, large-scale replication studies have demonstrated that replicability is far from favorable, across multiple scientific fields. Here, I evaluate this literature and describe contributing factors including the prevalence of questionable research practices (QRPs), misunderstanding of p-values, and low statistical power. I subsequently discuss how these issues manifest specifically in preclinical neuroscience research. I conclude that these problems are multifaceted and difficult to solve, relying on the actions of early and late career researchers, funding sources, academic publishers, and others. I assert that any viable solution to the problem of substandard replicability must include changing academic incentives, with adoption of registered reports being the most immediately impactful and pragmatic strategy. For animal research in particular, comprehensive reporting guidelines that document potential sources of sensitivity for experimental outcomes is an essential addition.

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Strain Differences in Responsiveness to Repeated Restraint Stress Affect Remote Contextual Fear Memory and Blood Transcriptomics

Cited by 7 publications

References 55 publications

Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3

Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3

The Wistar Kyoto Rat: A Model of Depression Traits

Questionable Research Practices, Low Statistical Power, and Other Obstacles to Replicability: Why Preclinical Neuroscience Research Would Benefit from Registered Reports

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