Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats

Farrell, Mollee R.; Holland, Freedom H.; Shansky, Rebecca M.; Brenhouse, Heather C.

doi:10.1016/j.bbr.2016.05.009

Cited by 74 publications

(45 citation statements)

References 55 publications

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“…Using another ELS paradigm, i.e. maternal separation during the entire postnatal period, it was reported that stressed females, but not males had increased infralimbic mPFC apical dendritic branch number and length at PND40 compared to controls (Farrell, Holland, Shansky, & Brenhouse, 2016). Together, these studies suggest that ELS, and in particular LBN, tends to hamper higher order cognitive functions while enhancing the emotional aspects, in particular expression of conditioned fear (Krugers, et al, 2016).…”

Section: Proximal (Neonatal) and Distal (Adult) Phenotypes Resultimentioning

confidence: 99%

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Walker

Bath

Joëls

et al. 2017

Stress

273

322

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The immediate and long term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current population, and for generations to come.

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Section: Proximal (Neonatal) and Distal (Adult) Phenotypes Resultimentioning

confidence: 99%

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Walker

Bath

Joëls

et al. 2017

Stress

273

322

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“…While our data do not establish a cause‐effect relationship between increased dendritic arborization and impaired social behavior, they add to emerging evidence linking these two phenomena in juvenile animals. For example, early life stress caused by maternal separation increased apical dendritic branch number and length of pyramidal neurons in the medial prefrontal cortex of female juvenile rats, and these morphological outcomes coincided with deficits in social interactions . Similarly, in a model of endoplasmic reticulum stress, adult male mice exhibit decreased social behavior coincident with hyperconnectivity in the neural circuit from the medial prefrontal cortex to the dorsal hippocampus as measured by implanted depth electrodes .…”

Section: Discussionmentioning

confidence: 99%

Genetic mutations in Ca²⁺ signaling alter dendrite morphology and social approach in juvenile mice

Keil

Sethi

Wilson

et al. 2018

Genes Brain and Behavior

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Dendritic morphology is a critical determinant of neuronal connectivity, and calcium signaling plays a predominant role in shaping dendrites. Altered dendritic morphology and genetic mutations in calcium signaling are both associated with neurodevelopmental disorders (NDDs). In this study we tested the hypothesis that dendritic arborization and NDD-relevant behavioral phenotypes are altered by human mutations that modulate calcium-dependent signaling pathways implicated in NDDs. The dendritic morphology of pyramidal neurons in CA1 hippocampus and somatosensory cortex was quantified in Golgi-stained brain sections from juvenile mice of both sexes expressing either a human gain-of-function mutation in ryanodine receptor 1 (T4826I-RYR1), a human CGG repeat expansion (170-200 CGG repeats) in the fragile X mental retardation gene 1 (FMR1 premutation), both mutations (double mutation; DM), or wildtype mice. In hippocampal neurons, increased dendritic arborization was observed in male T4826I-RYR1 and, to a lesser extent, male FMR1 premutation neurons. Dendritic morphology of cortical neurons was altered in both sexes of FMR1 premutation and DM animals with the most pronounced differences seen in DM females. Genotype also impaired behavior, as assessed using the three-chambered social approach test. The most striking lack of sociability was observed in DM male and female mice. In conclusion, mutations that alter the fidelity of calcium signaling enhance dendritic arborization in a brain region- and sex-specific manner and impair social behavior in juvenile mice. The phenotypic outcomes of these mutations likely provide a susceptible biological substrate for additional environmental stressors that converge on calcium signaling to determine individual NDD risk.

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“…Furthermore, a reduction in D1 receptor expression on mPFC → NAc projections in adolescence is observed following maternal separation (Brenhouse et al, 2008, 2013), and may represent a depressive affect state (Freund et al, 2016). Chronic stress also reduces dendritic branching and/or spine density in mPFC and dorsomedial STR (including the NAc; Cook and Wellman, 2004; Dias-Ferreira et al, 2009; Liston et al, 2006; Radley et al, 2004; Taylor et al, 2014; but see Farrell et al, 2016). In contrast, chronic stress increases dendritic branching in OFC and dorsolateral STR, the latter of which is involved in habit-driven behaviors (Dias-Ferreira et al, 2009; Taylor et al, 2014).…”

Section: Etiology Of Substance Abuse and Relevance To Adolescencementioning

confidence: 99%

Sensitive periods of substance abuse: Early risk for the transition to dependence

Jordan

Andersen

2017

Developmental Cognitive Neuroscience

281

152

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Early adolescent substance use dramatically increases the risk of lifelong substance use disorder (SUD). An adolescent sensitive period evolved to allow the development of risk-taking traits that aid in survival; today these may manifest as a vulnerability to drugs of abuse. Early substance use interferes with ongoing neurodevelopment to induce neurobiological changes that further augment SUD risk. Although many individuals use drugs recreationally, only a small percentage transition to SUD. Current theories on the etiology of addiction can lend insights into the risk factors that increase vulnerability from early recreational use to addiction. Building on the work of others, we suggest individual risk for SUD emerges from an immature PFC combined with hyper-reactivity of reward salience, habit, and stress systems. Early identification of risk factors is critical to reducing the occurrence of SUD. We suggest preventative interventions for SUD that can be either tailored to individual risk profiles and/or implemented broadly, prior to the sensitive adolescent period, to maximize resilience to developing substance dependence. Recommendations for future research include a focus on the juvenile and adolescent periods as well as on sex differences to better understand early risk and identify the most efficacious preventions for SUD.

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Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats

Cited by 74 publications

References 55 publications

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Genetic mutations in Ca²⁺ signaling alter dendrite morphology and social approach in juvenile mice

Sensitive periods of substance abuse: Early risk for the transition to dependence

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Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats

Cited by 74 publications

References 55 publications

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Genetic mutations in Ca2+ signaling alter dendrite morphology and social approach in juvenile mice

Sensitive periods of substance abuse: Early risk for the transition to dependence

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Product

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Genetic mutations in Ca²⁺ signaling alter dendrite morphology and social approach in juvenile mice