Sex Differences in Risk and Resilience: Stress Effects on the Neural Substrates of Emotion and Motivation

Wellman, Cara L.; Bangasser, Debra A.; Bollinger, Justin L.; Coutellier, Laurence; Logrip, Marian L.; Moench, Kelly M.; Urban, Kimberly R.

doi:10.1523/jneurosci.1673-18.2018

Cited by 70 publications

(54 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Pretreatment with diazepam prior to repeated stress exposure may alter glutamate dynamics and E/I balance in the PFC, preventing the PFC from adapting its response to multiple stressors, according to a study in male rats (Bagley and Moghaddam, 1997). The male PFC may be better able to adapt to the effects of repeated stress exposure compared to the female PFC (Moench and Wellman, 2017;Wellman et al, 2018;Moench et al, 2019). Plasticity of the PFC following stress is important for resilience and recovery, and chronic stress may impair prefrontal plasticity especially in females.…”

Section: Discussionmentioning

confidence: 99%

“…If this is the case, females may be more susceptible to a "second hit" of a novel stressor: while prior chronic stress exposure blunts novel acute stress-induced neuronal activation in males, females may have a more exaggerated response to subsequent stressors. Therefore, dendritic retraction may be an adaptive, protective mechanism against initial stress exposure that males employ but females do not, rendering females more susceptible to chronic stress and emotional dysfunction (Moench and Wellman, 2017;Wellman et al, 2018). Supporting the hypothesis that females are more susceptible to a "second hit" of stress, chronically stressed female rats given a rest period show enhanced activity in limbic brain regions following a novel acute stressor compared to their unstressed counterparts.…”

Section: Prefrontal E/i Balance In Emotional Disorders and Chronic Stmentioning

confidence: 96%

“…The rodent studies cited above were conducted exclusively in male mice, and the human studies did not analyze sex differences. There is increasing evidence to suggest that the PFC of females may respond differently to stress (Wellman et al, 2018). Females show unique, estrogen-dependent patterns of pyramidal cell dendritic remodeling in the PFC and PFC-amygdala connections following chronic stress (Garrett and Wellman, 2009;Shansky et al, 2010).…”

Section: Prefrontal E/i Balance In Emotional Disorders and Chronic Stmentioning

confidence: 99%

“…Females show unique, estrogen-dependent patterns of pyramidal cell dendritic remodeling in the PFC and PFC-amygdala connections following chronic stress (Garrett and Wellman, 2009;Shansky et al, 2010). Following chronic stress, males show the above-mentioned dendritic retraction in the PFC, but females do not (or even show dendritic hypertrophy), possibly due to protective effects of estrogen (Wei et al, 2014;Wellman et al, 2018).…”

Section: Prefrontal E/i Balance In Emotional Disorders and Chronic Stmentioning

confidence: 99%

See 3 more Smart Citations

Prefrontal excitatory/inhibitory balance in stress and emotional disorders: Evidence for over-inhibition

Page

Coutellier

2019

Neuroscience & Biobehavioral Reviews

Self Cite

146

View full text Add to dashboard Cite

Chronic stress-related emotional disorders like anxiety and depression involve imbalances between the excitatory glutamatergic system and the inhibitory γaminobutyric acid (GABA) system in the prefrontal cortex (PFC). However, the precise nature and trajectory of excitatory/inhibitory (E/I) imbalances in these conditions is not clear, with the literature reporting glutamatergic and GABAergic findings that are at times contradictory and inconclusive. In this dissertation, I propose and discuss the hypothesis that chronic stress-induced anxiety involves hypoactivity of the PFC due to increased inhibition, mediated in part through increased activity of prefrontal parvalbumin (PV)-expressing inhibitory interneurons. Differing sensitivity of the prefrontal GABAergic system and PV neurons to chronic stress may also underlie sex differences in the prevalence of anxiety disorders, with women presenting with anxiety at higher rates than men. I first present evidence that chronic stress increases the activity of prefrontal PV neurons, and that increased activity of this cell population induces hypoactivity of the PFC. Furthermore, increasing prefrontal PV cell activity using DREADDs (designer receptors exclusively activated by designer drugs) induces anxietylike behaviors specifically in females (Chapter 2). However, acute inhibition of prefrontal PV cells using DREADDs is insufficient to rescue stress-induced anxiety-like behavior, though it does modulate activity and synaptic plasticity in the PFC in a sex

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Prefrontal E/i Balance In Emotional Disorders and Chronic Stmentioning

confidence: 96%

Section: Prefrontal E/i Balance In Emotional Disorders and Chronic Stmentioning

confidence: 99%

Section: Prefrontal E/i Balance In Emotional Disorders and Chronic Stmentioning

confidence: 99%

See 2 more Smart Citations

Prefrontal excitatory/inhibitory balance in stress and emotional disorders: Evidence for over-inhibition

Page

Coutellier

2019

Neuroscience & Biobehavioral Reviews

Self Cite

146

View full text Add to dashboard Cite

show abstract

“…Dysfunction of the PFC has been implicated in the pathophysiology of stress‐linked disorders (e.g., Merriam, Thase, Haas, Keshavan, & Sweeney, ; Milad et al, ; Rajkowska, O'Dwyer, Teleki, Stockmeier, & Miguel‐Hidalgo, ). PFC modulates several processes, including executive function and emotion regulation, that are impaired in many stress‐sensitive disorders (Wellman et al, ). In addition, the PFC, along with other corticolimbic brain regions, helps to coordinate the body's physiological response to stress through feedback to the HPA axis (Diorio, Viau, & Meaney, ; McKlveen, Myers, & Herman, ).…”

Section: Introductionmentioning

confidence: 99%

Social instability in adolescence differentially alters dendritic morphology in the medial prefrontal cortex and its response to stress in adult male and female rats

Breach

Moench

Wellman

2019

Developmental Neurobiology

Self Cite

View full text Add to dashboard Cite

Adolescence is an important period for HPA axis development and synapse maturation and reorganization in the prefrontal cortex (PFC). Thus, stress during adolescence could alter stress-sensitive brain regions such as the PFC and may alter the impact of future stressors on these brain regions. Given that women are more susceptible to many stress-linked psychological disorders in which dysfunction of PFC is implicated, and that this increased vulnerability emerges in adolescence, stress during this time could have sex-dependent effects. Therefore, we investigated the effects of adolescent social instability stress (SIS) on dendritic morphology of Golgistained pyramidal cells in the medial PFC of adult male and female rats. We then examined dendritic reorganization following chronic restraint stress (CRS) with and without a rest period in adult rats that had been stressed in adolescence. Adolescent SIS conferred long-term alterations in prelimbic of males and females, whereby females show reduced apical length and basilar thin spine density and males show reduced basilar length. CRS in adulthood failed to produce immediate dendritic remodeling in SIS rats. However, CRS followed by a rest period reduced apical dendritic length and increases mushroom spine density in adolescently stressed adult males. Conversely, CRS followed by rest produced apical outgrowth and decreased mushroom spine density in adolescently stressed adult females. These results suggest that stress during adolescence alters development of the PFC and modulates stressinduced dendritic changes in adulthood. K E Y W O R D Sadolescent, chronic restraint stress, neuronal morphology, sex differences, social stress 840 | BREACH Et Al.How to cite this article: Breach MR, Moench KM, Wellman CL. Social instability in adolescence differentially alters dendritic morphology in the medial prefrontal cortex and its response to stress in adult male and female rats. Develop Neurobiol.

show abstract

Oestrogens: Structure, Mechanisms of Action and Role in Mood and Cognition

Almeida

Patchev²

2020

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Oestrogens are steroid hormones that act through specific receptors in the brain to influence a variety of functions, including mood and cognition. The best‐known and most potent endogenous oestrogen is 17β‐oestradiol (17β‐E 2 ). Oestrogen actions in the brain include alterations of neuronal excitability, neurotransmitter synthesis and metabolism, neuronal development, morphology and survival as well as connectivity between different brain areas so as to generate behaviours that are appropriate to internal (physiological) and external (environmental) demands. In the so‐called classical mode of action, oestrogens bind to specific receptors located in the cell nucleus that regulate gene transcription and ultimately protein synthesis. Such receptors are widely distributed in the brain and peripheral tissues such as breast, uterus, bone, liver and heart. Oestrogen actions mediated by nuclear receptors only become detectable after several hours. In contrast, more recently described membrane‐bound receptors allow oestrogens to rapidly alter the excitability of neuronal and nonneuronal membranes. Thus, oestrogens have the potential to influence brain function through slow‐ and/or fast‐acting modes. Knowledge about how and what brain structures and functions are responsive to oestrogens over the entire lifespan is key to informing future improvements in women's health, from adolescence through to old age. Oestrogens are steroid hormones that modulate neuronal structure, activity and function; the term ‘oestrogen’ refers to both naturally produced hormones and synthetic analogues. Modern industrial products contain a variety of chemicals with oestrogen‐like properties. These so‐called endocrine disruptor compounds are considered to be environmental health hazards. Oestrogen secretion starts during early development, varies cyclically from puberty onwards and gradually diminishes with age (menopause in women). Oestrogens and oestrogen‐like compounds bind to oestrogen receptors located in either the plasma membrane or cell nucleus that lead to rapid changes in neuronal excitability and slow‐onset changes in protein synthesis, respectively. Both the rapid and slow modes of oestrogen action contribute to the regulation of complex behaviours such as mood and cognition. Oestrogens have wide therapeutic applications, for example in contraception and management of postmenopausal symptoms, but their prescription requires careful tailoring to individual needs and potential risk factors. Phytoestrogens are natural (plant) compounds. Although they are widely promoted in alternative medicine, their efficacy is questionable.

show abstract

Sex Differences in Risk and Resilience: Stress Effects on the Neural Substrates of Emotion and Motivation

Cited by 70 publications

References 128 publications

Prefrontal excitatory/inhibitory balance in stress and emotional disorders: Evidence for over-inhibition

Prefrontal excitatory/inhibitory balance in stress and emotional disorders: Evidence for over-inhibition

Social instability in adolescence differentially alters dendritic morphology in the medial prefrontal cortex and its response to stress in adult male and female rats

Oestrogens: Structure, Mechanisms of Action and Role in Mood and Cognition

Contact Info

Product

Resources

About