Early Life Stress in Rodents: Animal Models of Illness or Resilience?

Murthy, Sahana; Gould, Elizabeth

doi:10.3389/fnbeh.2018.00157

Cited by 98 publications

(68 citation statements)

References 55 publications

(70 reference statements)

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“…Chickens ( Gallus gallus ) artificially reared are more likely to develop behavioral problems than mother‐reared individuals (Edgar, Held, Jones, & Troisi, ). In rodents, unpredictability of maternally derived sensory signals provoke emotional and cognitive dysfunction in offspring (Baram et al, ), and globally neglect‐like environments in rat pups lead to long‐term depression‐like behavioral traits and to altered physiological and hormonal activity, and gut microbiota composition (Murthy & Gould, ; O'Mahony et al, ; Pryce, Rüedi‐Bettschen, Dettling, & Feldon, ).…”

Section: Introductionmentioning

confidence: 99%

Bushmeat trade consequences predict higher anxiety, restraint, and dominance in chimpanzees

Ortín

Úbeda

Garriga³

et al. 2019

Developmental Psychobiology

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More data are needed for a better understanding of the long‐term influence of wider and combined stressful events in chimpanzee personality development. We evaluated the effects of bushmeat trade outcomes on the personality development in 84 African sanctuary chimpanzees. The chimpanzees presented different backgrounds regarding maternal care, social exposure, and abuse. We evaluated personality traits in chimpanzees using the Cattell 16PF personality questionnaire, the first application of this questionnaire in this species. We found that chimpanzees were rated as higher in anxiety after long social deprivation during infancy and juvenility, and if high human exposure was experienced. Mother‐reared chimpanzees were rated as lower in restraint than hand‐reared chimpanzees. Finally, mother‐reared chimpanzees were rated as less dominant than hand‐reared chimpanzees and rated higher when they had experienced severe mistreatment. Results suggest a wide range of possible stressful events could be potentially shaping rescued chimpanzees’ personality and demonstrating the detrimental outcomes and consequences of the bushmeat and pet trade.

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Section: Introductionmentioning

confidence: 99%

Bushmeat trade consequences predict higher anxiety, restraint, and dominance in chimpanzees

Ortín

Úbeda

Garriga³

et al. 2019

Developmental Psychobiology

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“…Nonetheless, more than 60 years ago, Levine demonstrated that mild stress exposure can lead to an inoculation effect in the adult rat, making it more resilient to stressors 53 . These findings were later validated in mice and squirrel monkeys 54,55 . In line with this notion, in our study hopless larvae exhibited increased anxiety-like behavior in the light-dark preference test and reduced habituation to repeated light-to-dark transitions.…”

Section: Discussionmentioning

confidence: 71%

Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior

Biran

Gliksberg

Shirat

et al. 2020

Preprint

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25The pituitary adenylate cyclase-activating polypeptide receptor (PAC1, also known as 26 ADCYAP1R1) is associated with post-traumatic stress disorder and modulation of 27 stress response in general. Alternative splicing of PAC1 results in multiple gene 28 products, which differ in their mode of signalling and tissue distribution. However, 29 the roles of distinct splice variants in the regulation of stress behavior is poorly 30 understood. Alternative splicing of a short exon, which is known as the "hop 31 cassette", occurs during brain development and in response to stressful challenges. To 32 examine the function of this variant, we generated a splice-specific zebrafish mutant 33 lacking the hop cassette, which we designated 'hopless'. We show that hopless mutant 34 larvae display increased anxiety-like behavior, including reduced dark exploration and 35 impaired habituation to dark exposure. Conversely, adult hopless mutants displayed 36 superior ability to rebound from an acute stressor, as they exhibited reduced anxiety-37 like responses to an ensuing novelty stress. We propose that the developmental loss of 38 a specific PAC1 splice variant mimics prolonged mild stress exposure, which in the 39 long term, predisposes the organism's stress response towards a resilient phenotype. 40Our study presents a unique genetic model demonstrating how early-life state of 41 anxiety paradoxically correlates with reduced stress susceptibility in adulthood. 42 43 44 45 46 47 48 49 50 51 52 53 PAC1 (a.k.a. Adcyap1r1) is a G-protein coupled receptor (GPCR) that serves as the 54 high-affinity receptor for pituitary adenylate cyclase-activating polypeptide (PACAP). 55 PAC1 has pleiotropic functions and was demonstrated to be involved in the regulation 56 of several homeostatic processes including metabolic rate and food consumption 1,2 , 57 circadian rhythm 3 and, in particular, stress response 4,5 . Intracerebroventricular injection 58 of PACAP increased phosphorylated cyclic AMP response element binding protein 59(pCREB) and CRH immunoreactivity in the rat paraventricular nucleus 6 . PACAP 60 knockout mice display blunted hypothalamic CRH levels in response to restraint 61 challenge 7 . PACAP/PAC1 signaling was also associated with hypothalamo-pituitary-62 adrenal activity and stress-related behaviors in humans and rodents 5,8,9 . Furthermore, 63 this pathway was correlated with stress-related risky behaviors in human and 64 rodents 10,11 . Overall, these findings support positive stress regulation by PAC1; yet, 65 some data suggest that it may also act to suppress stress phenotypes 4,12 . 66It has been suggested that genetic vulnerability to post-traumatic stress disorder 67 (PTSD) may depend on PAC1 expression and single-nucleotide polymorphism (SNP) 68 in the PAC1 gene. Ressler et al. demonstrated that a specific PAC1 genotype is strongly 69 correlated with susceptibility to PTSD in women, probably due to perturbed expression 70 of PAC1 resulting in impaired stress responses 13 . The same PAC1 SNP was associat...

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“…Moreover, the inability to compare two stress paradigms across labs due to a host of confounding factors (e.g., time and duration of the stressor, time (age and time of day) of assessment, light-dark cycle, laboratoryspecific environmental features, rodent strain, individual differences in maternal care, etc.) further blurs our understanding of what these paradigms are modeling 8 . Accordingly, it is critical and timely to compare the specific effects of these models.…”

Section: Aberrant Maternal Care As An Early Life Stressormentioning

confidence: 99%

“…Animal models are invaluable for understanding the neural mechanisms by which these aberrations may occur; they allow us to interrogate specific, anatomical and cellular circuits at the macro and micro scales as well as perform highly controlled experiments that better link such circuits to functional outcomes like behaviors 6 . Moreover, better characterizing our current models may enhance translatability by clarifying which functions each paradigm best models 7,8 .…”

Section: Aberrant Maternal Care As An Early Life Stressormentioning

confidence: 99%

“…Though impairments are traditionally noted, many studies find no differences or even note improvements in behaviors following early life stress. In fact, limited bedding and maternal separation have more recently garnered interest as models of resilience 8,17,18 . The variable effects of these models can be diffuse and difficult to understand.…”

Section: Aberrant Maternal Care As An Early Life Stressormentioning

confidence: 99%

See 1 more Smart Citation

Differential Effects of Two Early Life Stress Paradigms on Cerebellar-Dependent Delay Eyeblink Conditioning

Moussa-Tooks

Hetrick

Green

2020

Preprint

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Word Count: 167 (200 limit) Text Body Word Count (including figure legends and acknowledgements): 4958 AbstractEarly life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature: (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study utilized delay eyeblink conditioning, an associative learning task with a well-defined cerebellar circuit, to compare the behavioral effects of standard limited bedding (postnatal day 2-9, n=15) and maternal separation (60 minutes per day during postnatal day 2-14, n=13) early life stress paradigms. Animals in all groups exhibited robust learning curves. Surprisingly, facilitated conditioning was observed in the maternal separation group. Rats that underwent limited bedding did not differ from the control or maternal separation groups on any conditioning measures. This study contributes to a clearer understanding of early life stress paradigms and the claims made about their mechanisms, which if better clarified can be properly leveraged to increase translational value.

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Early Life Stress in Rodents: Animal Models of Illness or Resilience?

Cited by 98 publications

References 55 publications

Bushmeat trade consequences predict higher anxiety, restraint, and dominance in chimpanzees

Bushmeat trade consequences predict higher anxiety, restraint, and dominance in chimpanzees

Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior

Differential Effects of Two Early Life Stress Paradigms on Cerebellar-Dependent Delay Eyeblink Conditioning

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