Stress and the Adolescent Brain

Coming of Age ◽  
2019 ◽  
pp. 96-119
Author(s):  
Cheryl L. Sisk ◽  
Russell D. Romeo
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Stress Responses ◽  
Stress Reactivity ◽  
Recovery Period ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Functional Changes ◽  
Psychological Stressors

Chapter 7 considers stress as a modulator of adolescent development. It starts with an overview of the key hormones in the hypothalamic–pituitary–adrenal (HPA) axis and describes responses of the HPA axis and the sympathetic nervous system to stress. The HPA stress response is somewhat different in adolescents compared with adults; adolescents often show heightened stress reactivity and a protracted recovery period after psychological stressors compared to adults. The chapter then reviews research on chronic stress-induced anatomical and functional changes in the hippocampus, prefrontal cortex, and amygdala, three brain regions involved in regulation of the HPA axis and modulation of stress responses. Stress-induced changes in these brain regions include dendritic complexity of pyramidal cells, attenuated long-term potentiation, attention deficits, and changes in fear and depressive-like behaviors; these changes may be long-lasting. The perfect storm alludes to the alignment of three features of adolescence that together may render the adolescent brain especially vulnerable to effects of chronic stress: (a) The quality and quantity of stressors is different during adolescence than in adulthood; (b) stress reactivity is higher during adolescence; and (c) the hippocampus, prefrontal cortex, and amygdala are sensitive to stress hormones and are still developing during adolescence. However, the developing adolescent brain may be more resilient to insult, more responsive to interventions, and more buffered by social support systems.

Limbic Pathways to Stress Control

2016 ◽  
Author(s):  
James P. Herman
Keyword(s):  
Neural Networks ◽  
Prefrontal Cortex ◽  
Stress Response ◽  
Hpa Axis ◽  
Stress Responses ◽  
Physiological Stress ◽  
Brain Regions ◽  
Subcortical Structures ◽  
Stress Control ◽  
Stress Activation

Appropriate control of the HPA (hypothalamo-pituitary-adrenocortical axis) is required for adaptation to physiological and environmental challenges. Inadequate control is linked to numerous stress-related pathologies, including PTSD, highlighting its importance in linking physiological stress responses with behavioral coping strategies. This chapter highlights neurocircuit mechanisms underlying HPA axis adaptation and pathology. Control of the HPA stress response is mediated by the coordinated activity of numerous limbic brain regions, including the prefrontal cortex, hippocampus, and amygdala. In general, hippocampal output inhibits anticipatory HPA axis responses, whereas amygdala subnuclei participate in stress activation. The prefrontal cortex plays an important role in inhibition of context-dependent stress responses. These regions converge on subcortical structures that relay information to paraventricular nucleus corticotropin-releasing hormone neurons, controlling the magnitude and duration of HPA axis stress responses. The output of these neural networks determines the net effect on glucocorticoid secretion, both within the normal adaptive range and in pathological circumstances.

scholarly journals Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Meltem Weger ◽  
Daniel Alpern ◽  
Antoine Cherix ◽  
Sriparna Ghosal ◽  
Jocelyn Grosse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Prefrontal Cortex ◽  
Mitochondrial Dysfunction ◽  
Chronic Stress ◽  
Mitochondrial Gene ◽  
Brain Regions ◽  
Mitochondrial Gene Expression ◽  
Data Set ◽  
A Genome

Abstract Mitochondrial dysfunction was highlighted as a crucial vulnerability factor for the development of depression. However, systemic studies assessing stress-induced changes in mitochondria-associated genes in brain regions relevant to depression symptomatology remain scarce. Here, we performed a genome-wide transcriptomic study to examine mitochondrial gene expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) of mice exposed to multimodal chronic restraint stress. We identified mitochondria-associated gene pathways as most prominently affected in the PFC and with lesser significance in the NAc. A more detailed mitochondrial gene expression analysis revealed that in particular mitochondrial DNA-encoded subunits of the oxidative phosphorylation complexes were altered in the PFC. The comparison of our data with a reanalyzed transcriptome data set of chronic variable stress mice and major depression disorder subjects showed that the changes in mitochondrial DNA-encoded genes are a feature generalizing to other chronic stress-protocols as well and might have translational relevance. Finally, we provide evidence for changes in mitochondrial outputs in the PFC following chronic stress that are indicative of mitochondrial dysfunction. Collectively, our work reinforces the idea that changes in mitochondrial gene expression are key players in the prefrontal adaptations observed in individuals with high behavioral susceptibility and resilience to chronic stress.

scholarly journals Environment and Behavior: Neurochemical Effects of Different Diets in the Calf Brain

Animals ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 358 ◽  
Author(s):  
Angelo Peli ◽  
Annamaria Grandis ◽  
Marco Tassinari ◽  
Paolo Famigli Bergamini ◽  
Claudio Tagliavia ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Paraventricular Nucleus ◽  
Stress Responses ◽  
Control Diet ◽  
Brain Regions ◽  
Diet Group ◽  
Stressful Events ◽  
Solitary Tract ◽  
Milk Diet ◽  
Housing Systems

Calves reared for the production of white veal are subjected to stressful events due to the type of liquid diet they receive. Stress responses are mediated by three main stress-responsive cerebral regions: the prefrontal cortex, the paraventricular nucleus of the hypothalamus, and the nucleus of the solitary tract of the brainstem. In the present study, we have investigated the effects of different diets on these brain regions of ruminants using immunohistochemical methods. In this study, 15 calves were used and kept in group housing systems of five calves each. They were fed with three different diets: a control diet, a milk diet, and a weaned diet. Brain sections were immunostained to evaluate the distribution of neuronal nitric oxide synthase and myelin oligodendrocyte glycoprotein immunoreactivity in the prefrontal cortex; the expression of oxytocin in the paraventricular nucleus; and the presence of c-Fos in the A2 group of the nucleus of the solitary tract. The main results obtained indicate that in weaned diet group the oxytocin activity is lower than in control diet and milk diet groups. In addition, weaning appears to stimulate myelination in the prefrontal cortex. In summary, this study supports the importance of maintaining a nutritional lifestyle similar to that occurring in natural conditions.

scholarly journals Parental buffering in the context of poverty: positive parenting behaviors differentiate young children's stress reactivity profiles

2020 ◽  
Vol 32 (5) ◽  
pp. 1778-1787
Author(s):  
Samantha M. Brown ◽  
Lisa J. Schlueter ◽  
Eliana Hurwich-Reiss ◽  
Julia Dmitrieva ◽  
Elly Miles ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Low Income ◽  
Stress Responses ◽  
Stress Reactivity ◽  
Growth Models ◽  
Parenting Behaviors ◽  
Time Of Day ◽  
Positive Parenting ◽  
Cortisol Reactivity ◽  
Hpa Axis Functioning

AbstractExperiencing poverty increases vulnerability for dysregulated hypothalamic–pituitary–adrenal (HPA) axis functioning and compromises long-term health. Positive parenting buffers children from HPA axis reactivity, yet this has primarily been documented among families not experiencing poverty. We tested the theorized power of positive parenting in 124 parent–child dyads recruited from Early Head Start (Mage = 25.21 months) by examining child cortisol trajectories using five samples collected across a standardized stress paradigm. Piecewise latent growth models revealed that positive parenting buffered children's stress responses when controlling for time of day, last stress task completed, and demographics. Positive parenting also interacted with income such that positive parenting was especially protective for cortisol reactivity in families experiencing greater poverty. Findings suggest that positive parenting behaviors are important for protecting children in families experiencing low income from heightened or prolonged physiologic stress reactivity to an acute stressor.

scholarly journals fMRI analysis of MCP-1 induced prefrontal cortex neuronal dysfunction in depressive cynomolgus monkeys

2020 ◽  
Author(s):  
Weixin Yan ◽  
Di Zhao ◽  
Kai Liu ◽  
Yanjia Deng ◽  
Lingpeng Xie ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Brain Area ◽  
Recovery Period ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cynomolgus Monkeys ◽  
Functional Changes

Abstract Background Depression is a serious mental illness, which is one of the main causes of disability at present. The cause and location of depression are still unclear. The purpose of this study is to establish a stable and reliable model of non-human primate depression, and further confirm the significance of neuritis in the pathogenesis of depression by combining in vivo and in vitro experiments. Methods We simulated the environment of human depression and established a cynomolgus monkeys depression model by pro-depressive prodedure (PDP). The model was evaluated by behavioral test and neurotransmitter detection, and the important functional changes of brain area were detected by Functional magnetic resonance imaging (fMRI). Abnormal inflammatory factors in serum and cerebrospinal fluid (CSF) were determined by multi factor kit. In addition, the mechanism was further verified by stereotactic injection of inflammatory factor antagonists into mouse prefrontal cortex(PFC) and cell experiments. Results Here we found that a 12-week exposure to PDP can effectively induce the depressive behaviors of cynomolgus monkeys. PDP increases the time of depressive-like and anxious-like behaviors and decreases locomotor and exploratory behaviors, which were maintained after a 4-week recovery period. PDP lowers the serum serotonin (5-HT), brain-derived neurotrophic factor (BDNF) level at the end of the procedure. FMRI can reflect the state of brain function noninvasively based on the level of blood oxygen. The results demonstrate that fALFF signaling is downregulated in PFC. The downregulation of BDNF and NeuN(Neuronal nuclei antigen) in PFC are observed in depressive monkeys. At the same time, it was found that contents of the monocyte chemoattractant protein-1 (MCP-1) in serum, CSF and PFC are increased in cynomolgus monkeys receiving PDP treatment. Furthermore, we found that MCP-1 receptor antagonist (CCR2-RA-[R]) can significantly reduce the susceptibility of depression in mice and increase the expression of BDNF in serum and PFC of depressed mice and blocked the downregulation of MCP-1 on the expression of BDNF in SHSY-5Y cells. Conclusions In conclusion, PDP induces cynomolgus monkeys depression by secreting MCP-1 to impair the neurotrophic function of 5-HT in PFC. PDP is a satisfying method to establish inducible depressive model in cynomolgus monkeys.

scholarly journals Sex-specific blood-brain barrier alterations and vascular biomarkers underlie chronic stress responses in mice and human depression

2021 ◽  
Author(s):  
Laurence Dion-Albert ◽  
Alice Cadoret ◽  
Ellen Doney ◽  
Fernanda Neutzling Kaufmann ◽  
Katarzyna A. Dudek ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Chronic Stress ◽  
Stress Responses ◽  
Social Stress ◽  
Brain Regions ◽  
Brain Barrier ◽  
Social Avoidance ◽  
Morphological Alterations ◽  
Blood Brain ◽  
Vascular Biomarkers

Prevalence, symptoms, and treatment of depression all point toward major sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice however it remains unknown if it contributes to this sexual dimorphism. Here, we report that chronic social and subchronic variable stress promoted sex-specific blood-brain barrier (BBB) molecular and morphological alterations in mood-related brain regions. Viral-mediated functional manipulation leading to a targeted disruption of the BBB induced anxiety- and depression-like behaviors including social avoidance and anhedonia. Endothelium cell-specific transcriptomic profiling revealed key pathways and novel genes involved in maladaptive stress responses vs resilience. We also confirmed BBB leakiness in the brain of stressed females which led us to explore and identify circulating vascular biomarkers of chronic stress that could inform on diagnosis and treatment. Importantly, these pre-clinical findings were validated in human blood and postmortem brain samples from depressed women, thus highlighting their translational value. By revealing a sex-specific causal role of BBB dysfunction in stress responses and depression, our results implicate vascular impairment as a major factor underlying mood disorders.

scholarly journals Chemogenetic Inhibition of Infralimbic Prefrontal Cortex GABA-ergic Parvalbumin Interneurons Attenuates Chronic Stress Adaptions in Male Mice

2019 ◽  
Author(s):  
Nawshaba Nawreen ◽  
Rachel Morano ◽  
Parinaz Mahbod ◽  
Evelin M. Cotella ◽  
Khushali Dalal ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Stress Responses ◽  
Acute Stress ◽  
Forced Swim Test ◽  
Designer Drugs ◽  
Gabaergic Interneurons ◽  
Coping Behaviors ◽  
Passive Coping ◽  
Parvalbumin Interneurons

ABSTRACTHypofunction of the prefrontal cortex (PFC) contributes to stress-related neuropsychiatric illnesses. Mechanisms leading to prefrontal hypoactivity remain to be determined. Prior evidence suggests that enhanced activity of parvalbumin (PV) expressing GABAergic interneurons (INs) play a role in chronic stress related pathologies. In this study, the role of PFC PV INs in stress related phenotypes were explored using Cre inducible inhibitory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). Mice were first tested in the tail suspension test (TST) to determine the effects of PV IN inhibition during acute stress. Following this, the long term impact of PV IN inhibition during chronic variable stress (CVS) was tested in the forced swim test (FST). Acute PV IN inhibition reduced active (struggling) and increased passive coping behaviors (immobility) in the TST. In contrast, inhibition of PV INs during CVS increased active and reduced passive coping behaviors in the FST. Moreover, chronic inhibition of PV INs attenuated CVS-induced changes in Fos expression in the prelimbic cortex, basolateral amygdala and ventrolateral periaqueductal gray and also prevented adrenal hypertrophy and body weight loss associated with chronic stress. Our results suggest differential roles of PV INs to acute vs chronic stress, indicative of distinct biological mechanisms underlying acute vs. chronic stress responses. Our results also indicate a role for PV INs in driving chronic stress adaptation and support literature evidence suggesting cortical GABAergic interneurons as a therapeutic target in stress related diseases.SIGNIFICANCEStress related diseases are associated with prefrontal hypoactivity, the mechanism of which is currently not known. In this study we showed that by inhibiting prefrontal GABA-ergic Parvalbumin interneurons (PV INs) using DREADDs, we can attenuate some of chronic stress related phenotypes. Additionally, we showed that modulation of PV IN activity during acute vs chronic stress had opposing effects on stress coping strategies, suggesting different underlying mechanisms behind acute vs chronic stress paradigms. Our findings indicate that GABA-ergic PV INs may be involved in driving stress related phenotypes and thereby an important target for treatment of stress-related illnesses. Our data suggest that reducing PV IN activity to promote prefrontal output may be an effective treatment strategy for stress related disorders.

scholarly journals Jiao-Tai-Wan Ameliorates Depressive-Like Behavior through the A1R Pathway in Ovariectomized Mice after Unpredictable Chronic Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Lina Xiang ◽  
Yuan Feng ◽  
Qianqian Hu ◽  
Jiahui Zhu ◽  
Ren Ye ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Locomotor Activity ◽  
Chronic Stress ◽  
Forced Swim Test ◽  
Brain Regions ◽  
Depression Symptoms ◽  
Tail Suspension ◽  
Ovariectomized Mice ◽  
Forced Swim ◽  
Menopausal Depression

Objective. This study was aimed at observing the effect Jiao-Tai-Wan in menopausal depression. Methods. In this paper, we used ovariectomized mice subjected to chronic unpredictable stress as a menopausal depression model. After the chronic stress, mice were administrated with JTW (3.3 and 6.6mg/kg) and imipramine (10 mg/kg) for 14 days. On the 14th day, mice were subjected to the behavior test like the forced swim test, tail suspension test, and locomotor activity or were sacrificed to assess the protein changes in different brain regions. Results. The administration of JTW at doses of 3.3 and 6.6mg/kg (p.o.) significantly shortened the duration of immobility in forced swim and tail suspension tests. There was no obvious difference in locomotor activity among all the groups. The western blot analysis data indicated that treatment with JTW (3.3 and 6.6 mg/kg, p.o.) prominently increased the A1R protein and the downstream protein ERK1/2 levels in the prefrontal cortex and hippocampus. However, the administration of JTW did not influence c-Fos protein in either the prefrontal cortex or hippocampus. Conclusion. Our findings suggest that JTW plays a vital role in ameliorating menopausal depression symptoms in the A1R-ERK1/2 pathway in the prefrontal cortex and hippocampus.

scholarly journals Chronic stress induces sex-specific functional and morphological alterations in cortico-accumbal and cortico-tegmental pathways

2020 ◽  
Author(s):  
Thibault P. Bittar ◽  
Mari Carmen Pelaez ◽  
Jose Cesar Hernandez Silva ◽  
Francis Quessy ◽  
Andrée-Anne Lavigne ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Stress Responses ◽  
Morphological Alterations ◽  
Functional Changes ◽  
Behavioral Stress ◽  
Transcriptional Alterations ◽  
Males And Females ◽  
Chronic Variable Stress ◽  
The Impact ◽  
Dendritic Complexity

AbstractBackgroundThe medial prefrontal cortex (mPFC) is part of a complex circuit controlling stress responses by sending projections to different limbic structures including the nucleus accumbens (NAc) and ventral tegmental area (VTA). However, the impact of chronic stress on NAc- and VTA-projecting mPFC neurons is still unknown and the distinct contribution of these pathways to stress responses in males and females is unclear.MethodsBehavioral stress responses were induced by 21 days of chronic variable stress (CVS) in male and female C57BL6 mice. An inter-sectional viral approach was used to label both pathways and assess the functional, morphological, and transcriptional adaptations in NAc- and VTA-projecting mPFC neurons in stressed males and females. Using chemogenetic approaches, we modified neuronal activity of NAc-projecting mPFC neurons to decipher their contribution to stress phenotypes.ResultsCVS induced depressive-like behaviors in males and females. NAc- and VTA-projecting mPFC neurons exhibited sex-specific functional, morphological, and transcriptional alterations. The functional changes were more severe in females in NAc-projecting mPFC neurons while males exhibited more drastic reductions in dendritic complexity in VTA-projecting mPFC neurons after CVS. Finally, chemogenetic overactivation of the cortico-accumbal pathway triggered anxiety and behavioral despair in both sexes while its inhibition rescued the phenotype only in females.ConclusionsOur results suggest that by changing the activity of transcriptional programs controlling neuronal plasticity, CVS interferes with the morphological and synaptic properties of the cortico-accumbal and tegmental pathways differently in males and females contributing to the expression of anxiety and depressive-like behaviors distinctly in a sex-specific fashion.

scholarly journals Sexually divergent cortical control of affective-autonomic integration

2020 ◽  
Author(s):  
Tyler Wallace ◽  
Derek Schaeuble ◽  
Sebastian A. Pace ◽  
Morgan K. Schackmuth ◽  
Shane T. Hentges ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Stress Responses ◽  
Stress Reactivity ◽  
Physiological Stress ◽  
Social Motivation ◽  
Cortical Control ◽  
Biological Mechanisms ◽  
Cardiovascular Stress

AbstractDepression and cardiovascular disease reduce quality of life and increase mortality risk. These conditions commonly co-occur with sex-based differences in incidence and severity. However, the biological mechanisms linking the disorders are poorly understood. In the current study, we hypothesized that the infralimbic (IL) prefrontal cortex integrates depression-related behaviors with the cardiovascular burden of chronic stress. In a rodent model, we utilized optogenetics during behavior and in vivo physiological monitoring to examine how the IL regulates affect, social motivation, neuroendocrine-autonomic stress reactivity, and the cardiac consequences of chronic stress. Our results indicate that IL glutamate neurons increase socio-motivational behaviors specifically in males. IL activation also reduced endocrine and cardiovascular stress responses in males, while increasing reactivity in females. Moreover, prior IL stimulation protected males from subsequent chronic stress-induced sympatho-vagal imbalance and cardiac hypertrophy. Our findings suggest that cortical regulation of behavior, physiological stress responses, and cardiovascular outcomes fundamentally differ between sexes.

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