Brain metabolic alterations in mice subjected to postnatal traumatic stress and in their offspring

Adverse environmental and social conditions early in life have a strong impact on health. They are major risk factors for mental diseases in adulthood and, in some cases, their effects can be transmitted across generations. The consequences of detrimental stress conditions on brain metabolism across generations are not well known. Using high-field (14.1 T) magnetic resonance spectroscopy, we investigated the neurochemical profile of adult male mice exposed to traumatic stress in early postnatal life and of their offspring, and of undisturbed control mice. We found that, relative to controls, early life stress-exposed mice have metabolic alterations consistent with neuronal dysfunction, including reduced concentration of N-acetylaspartate, glutamate and γ-aminobutyrate, in the prefrontal cortex in basal conditions. Their offspring have normal neurochemical profiles in basal conditions. Remarkably, when challenged by an acute cold swim stress, the offspring has attenuated metabolic responses in the prefrontal cortex, hippocampus and striatum. In particular, the expected stress-induced reduction in the concentration of N-acetylaspartate, a putative marker of neuronal health, was prevented in the cortex and hippocampus. These findings suggest that paternal trauma can confer beneficial brain metabolism adaptations to acute stress in the offspring.

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Early Life Stress Alters Gene Expression and Cytoarchitecture in the Prefrontal Cortex Leading to Social Impairment and Increased Anxiety

Frontiers in Genetics ◽

10.3389/fgene.2021.754198 ◽

2021 ◽

Vol 12 ◽

Author(s):

Noriyoshi Usui ◽

Yuta Ono ◽

Ryoko Aramaki ◽

Stefano Berto ◽

Genevieve Konopka ◽

...

Keyword(s):

Prefrontal Cortex ◽

Life Stress ◽

Early Life ◽

Histological Analysis ◽

Social Preference ◽

Early Life Stress ◽

Social Behaviors ◽

Social Impairment ◽

Strong Impact ◽

The Brain

Early life stress (ELS), such as abuse, neglect, and maltreatment, exhibits a strong impact on the brain and mental development of children. However, it is not fully understood how ELS affects social behaviors and social-associated behaviors as well as developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice until adolescence and investigated these behaviors and PFC characteristics in adolescent mice. We found the ELS induced social impairments in social novelty, social interaction, and social preference in adolescent mice. We also observed increases of anxiety-like behaviors in ELS mice. In histological analysis, we found a reduced number of neurons and an increased number of microglia in the PFC of ELS mice. To identify the gene associated with behavioral and histological features, we analyzed transcriptome in the PFC of ELS mice and identified 15 differentially expressed genes involved in transcriptional regulation, stress, and synaptic signaling. Our study demonstrates that ELS influences social behaviors, anxiety-like behaviors through cytoarchitectural and transcriptomic alterations in the PFC of adolescent mice.

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Investigating peripubertal stress and exogenous corticosterone as endogenous stimulators of brain metabolism

10.1101/2020.07.14.203067 ◽

2020 ◽

Author(s):

Nathalie Just

Keyword(s):

Life Stress ◽

Early Life ◽

Acute Stress ◽

Lactate Concentration ◽

Early Life Stress ◽

Resonance Spectroscopy ◽

Adult Rats ◽

Concentration Changes ◽

As Stress ◽

And Behavior

AbstractSubstantial research on the association between early-life stress and its long-lasting impact on lifetime mental health has been performed revealing that early-life environmental adversity strongly regulates brain function. Alterations of gene expression and behavior in the off-springs of paternally stressed rats were also revealed. However, the precise mechanisms underlying these changes remain poorly understood. Here, an improved characterization of these processes from investigations of the functional metabolism of animal models exposed to peripubertal stress (PS) is proposed. The ultimate goal of this study was to bring forward functional Magnetic Resonance Spectroscopy (fMRS) as a technique of interest for a better understanding of brain areas by endogenous stimulators such as stress. The present study evaluated, compared and classified effects of individual PS (iPS) and paternal PS (pPS) under corticosterone (CORT) challenge in the septal areas of adult rats. Acute stress was simulated by injection of CORT and metabolic concentration changes were analyzed as a function of time. Evaluation of Glucose and Lactate concentration changes allowed the classification of groups of rats using a Glc to Lac index. Moreover, metabolic responses of control rats (CC) and of pPS x iPS rats (SS) were similar while responses in pPS (SC) and iPS (CS) differed, revealing differential adaption of energetic metabolism and of glutamatergic neurotransmission. Findings have crucial interest for understanding the metabolic mechanisms underlying altered functional connectivity and neuronal plasticity in septal areas inducing increased aggressivity in early-life stressed rats.

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Metabolic alterations of the dorsolateral prefrontal cortex in sleep‐related hypermotor epilepsy: A proton magnetic resonance spectroscopy study

Journal of Neuroscience Research ◽

10.1002/jnr.24866 ◽

2021 ◽

Author(s):

Weina Wang ◽

Xintong Wu ◽

Xiaorui Su ◽

Huaiqiang Sun ◽

Qiaoyue Tan ◽

...

Keyword(s):

Prefrontal Cortex ◽

Magnetic Resonance ◽

Dorsolateral Prefrontal Cortex ◽

Proton Magnetic Resonance ◽

Proton Magnetic Resonance Spectroscopy ◽

Resonance Spectroscopy ◽

Spectroscopy Study ◽

Metabolic Alterations ◽

Magnetic Resonance Spectroscopy Study ◽

Dorsolateral Prefrontal

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Maternal Depression, Child Temperament, and Early-Life Stress Predict Never-Depressed Preadolescents’ Functional Connectivity During a Negative-Mood Induction

Clinical Psychological Science ◽

10.1177/21677026211016419 ◽

2021 ◽

pp. 216770262110164

Author(s):

Pan Liu ◽

Matthew R. J. Vandermeer ◽

Ola Mohamed Ali ◽

Andrew R. Daoust ◽

Marc F. Joanisse ◽

...

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Maternal Depression ◽

Life Stress ◽

Early Life ◽

Negative Emotion ◽

Negative Mood ◽

Emotion Processing ◽

Early Life Stress ◽

Cingulate Cortex

Understanding the development of depression can inform etiology and prevention/intervention. Maternal depression and maladaptive patterns of temperament (e.g., low positive emotionality [PE] or high negative emotionality, especially sadness) are known to predict depression. Although it is unclear how these risks cause depression, altered functional connectivity (FC) during negative-emotion processing may play an important role. We investigated whether maternal depression and age-3 emotionality predicted FC during negative mood reactivity in never-depressed preadolescents and whether these relationships were augmented by early-life stress. Maternal depression predicted decreased medial prefrontal cortex (mPFC)–amygdala and mPFC–insula FC but increased mPFC–posterior cingulate cortex (PCC) FC. PE predicted increased dorsolateral prefrontal cortex–amygdala FC, whereas sadness predicted increased PCC-based FC in insula, orbitofrontal cortex, and anterior cingulate cortex (ACC). Sadness was more strongly associated with PCC–insula and PCC–ACC FC as early stress increased. Findings indicate that early depression risks may be mediated by FC underlying negative-emotion processing.

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Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review

Brain Sciences ◽

10.3390/brainsci11060723 ◽

2021 ◽

Vol 11 (6) ◽

pp. 723

Author(s):

Evangelos Karanikas ◽

Nikolaos P. Daskalakis ◽

Agorastos Agorastos

Keyword(s):

Traumatic Stress ◽

Life Stress ◽

Redox State ◽

Stress Disorder ◽

Early Life Stress ◽

Circadian System ◽

Clinical Genetic ◽

Knowledge Growth ◽

Substantial Heterogeneity ◽

Pituitary Adrenal Axis

Traumatic stress may chronically affect master homeostatic systems at the crossroads of peripheral and central susceptibility pathways and lead to the biological embedment of trauma-related allostatic trajectories through neurobiological alterations even decades later. Lately, there has been an exponential knowledge growth concerning the effect of traumatic stress on oxidative components and redox-state homeostasis. This extensive review encompasses a detailed description of the oxidative cascade components along with their physiological and pathophysiological functions and a systematic presentation of both preclinical and clinical, genetic and epigenetic human findings on trauma-related oxidative stress (OXS), followed by a substantial synthesis of the involved oxidative cascades into specific and functional, trauma-related pathways. The bulk of the evidence suggests an imbalance of pro-/anti-oxidative mechanisms under conditions of traumatic stress, respectively leading to a systemic oxidative dysregulation accompanied by toxic oxidation byproducts. Yet, there is substantial heterogeneity in findings probably relative to confounding, trauma-related parameters, as well as to the equivocal directionality of not only the involved oxidative mechanisms but other homeostatic ones. Accordingly, we also discuss the trauma-related OXS findings within the broader spectrum of systemic interactions with other major influencing systems, such as inflammation, the hypothalamic-pituitary-adrenal axis, and the circadian system. We intend to demonstrate the inherent complexity of all the systems involved, but also put forth associated caveats in the implementation and interpretation of OXS findings in trauma-related research and promote their comprehension within a broader context.

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Impact of early-life stress on the medial prefrontal cortex functions – a search for the pathomechanisms of anxiety and mood disorders

Pharmacological Reports ◽

10.1016/s1734-1140(13)71506-8 ◽

2013 ◽

Vol 65 (6) ◽

pp. 1462-1470 ◽

Cited By ~ 25

Author(s):

Agnieszka Chocyk ◽

Iwona Majcher-Maślanka ◽

Dorota Dudys ◽

Aleksandra Przyborowska ◽

Krzysztof Wędzony

Keyword(s):

Prefrontal Cortex ◽

Mood Disorders ◽

Medial Prefrontal Cortex ◽

Life Stress ◽

Early Life ◽

Early Life Stress

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Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis

Journal of Affective Disorders ◽

10.1016/j.jad.2017.08.066 ◽

2018 ◽

Vol 225 ◽

pp. 422-428 ◽

Cited By ~ 60

Author(s):

Qingzhong Wang ◽

Richard C. Shelton ◽

Yogesh Dwivedi

Keyword(s):

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Life Stress ◽

Early Life ◽

Stress Disorder ◽

Meta Analysis ◽

Early Life Stress ◽

Post Traumatic Stress ◽

Major Depressive ◽

Post Traumatic

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Perceived life stress exposure modulates reward-related medial prefrontal cortex responses to acute stress in depression

Journal of Affective Disorders ◽

10.1016/j.jad.2015.03.035 ◽

2015 ◽

Vol 180 ◽

pp. 104-111 ◽

Cited By ~ 17

Author(s):

Poornima Kumar ◽

George M. Slavich ◽

Lisa H. Berghorst ◽

Michael T. Treadway ◽

Nancy H. Brooks ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Life Stress ◽

Acute Stress ◽

Stress Exposure

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Abstract P219: Mice Exposed To Early Life Stress Have Impaired Autonomic Activity At Baseline And In Response To Acute Stress In Adulthood

Hypertension ◽

10.1161/hyp.76.suppl_1.p219 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Megan K Rhoads ◽

Kasi C McPherson ◽

Keri M Kemp ◽

Bryan Becker ◽

Jackson Colson ◽

...

Keyword(s):

Cardiovascular Disease ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Acute Stress ◽

Low Frequency ◽

Early Life Stress ◽

Total Power ◽

Increased Risk ◽

Inactive Period

Early life stress (ELS) is an independent risk factor for the development of cardiovascular disease in adulthood in both humans and rodent models. Maternal separation and early weaning (MSEW), a model of ELS, produces mice with an increased risk of cardiovascular dysfunction in adulthood, despite resting blood pressures (BP), heart rates (HR), and body weights comparable to normally reared controls. Autonomic regulation of HR and BP is an important component of the homeostatic response to stress but has not been investigated in MSEW mice. We hypothesized that exposure to MSEW impairs autonomic function at baseline and in response to an acute psychosocial stressor in adult male mice. C57Bl/6J litters were randomly assigned to MSEW or normally reared control conditions. MSEW litters were separated from dams for 4 h on postnatal days (PDs) 2-5, 8 h on PDs 6-16, and weaned at PD 17. Control litters were undisturbed until weaning at PD 21. At 9 weeks old, telemeters were implanted in MSEW (n=16) and control mice (n=12). During cage switch stress (CSS), mice were moved to a soiled, unfamiliar cage for 4 h. HR, systolic BP (SBP), diastolic BP (DBP), and activity (monitored by telemetry) were similar between control and MSEW mice at baseline and during CSS (p>0.05, 2-way ANOVA). Spectral analysis of HR, SBP, and DBP indicated that HR variability (HRV) total power was lower in MSEW mice during the 12 h inactive period compared to controls (18.9±1.1 ms 2 vs. 27.5±3.1 ms 2 ; p=0.0033, 2-way ANOVA) at baseline. HRV low frequency (LF) power was also lower during the 12 h inactive period in MSEW mice (4.2±0.4 ms 2 vs.6.6±0.9 ms 2 ; p=0.009). At baseline, 12 h and 24 h DBP variability LF/high frequency (HF) ratio, normalized LF, and normalized HF power were lower in the MSEW group (p<0.05, all comparisons). During the final 90 minutes of CSS, MSEW mice had lower HRV total, LF, and HF power compared to controls (p<0.05); although HR, SBP, DBP, and activity remained similar between groups. These data suggest that MSEW mice have impaired autonomic control of HR and DBP and lack the ability to robustly respond and recover from an acute stressor. Reduced responsiveness of the autonomic nervous system may contribute to the increased risk of cardiovascular disease development in adult mice exposed to MSEW.

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