scholarly journals Early life stress reduces voluntary exercise and its prevention of diet-induced obesity and metabolic dysfunction in mice

2020 ◽  
Author(s):  
Olivia C. Eller-Smith ◽  
E. Matthew Morris ◽  
John P. Thyfault ◽  
Julie A. Christianson
Keyword(s):  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Wheel Running ◽  
Control Diet ◽  
Early Life Stress ◽  
Voluntary Exercise ◽  
Free Access ◽  
Mrna Levels ◽  
Diet Induced Obesity

AbstractThe development of obesity-related metabolic syndrome (MetS) involves a complex interaction of genetic and environmental factors. One environmental factor found to be significantly associated with MetS is early life stress (ELS). We have previously reported on our mouse model of ELS, induced by neonatal maternal separation (NMS), that displays altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased sensitivity in the urogenital organs, which was attenuated by voluntary wheel running. Here, we are using our NMS model to determine if ELS-induced changes in the HPA axis also influence weight gain and MetS. Naïve (non-stressed) and NMS male mice were given free access to a running wheel and a low-fat control diet at 4-weeks of age. At 16-weeks of age, half of the mice were transitioned to a high fat/sucrose (HFS) diet to investigate if NMS influences the effectiveness of voluntary exercise to prevent diet-induced obesity and MetS. Overall, we observed a greater impact of voluntary exercise on prevention of HFS diet-induced outcomes in naïve mice, compared to NMS mice. Although body weight and fat mass were still significantly higher, exercise attenuated fasting insulin levels and mRNA levels of inflammatory markers in epididymal adipose tissue in HFS diet-fed naïve mice. Only moderate changes were observed in exercised NMS mice on a HFS diet, although this could partially be explained by reduced running distance within this group. Interestingly, sedentary NMS mice on a control diet displayed impaired glucose homeostasis and moderately increased pro-inflammatory mRNA levels in epididymal adipose, suggesting that early life stress alone impairs metabolic function and negatively impacts the therapeutic effect of voluntary exercise.

scholarly journals Voluntary Wheel Running Partially Attenuates Early Life Stress-Induced Neuroimmune Measures in the Dura and Evoked Migraine-Like Behaviors in Female Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Olivia C. Eller ◽  
Xiaofang Yang ◽  
Isabella M. Fuentes ◽  
Angela N. Pierce ◽  
Brittni M. Jones ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Significant Interaction ◽  
Wheel Running ◽  
Early Life Stress ◽  
Free Access ◽  
Voluntary Wheel Running ◽  
Withdrawal Threshold ◽  
Protein Levels ◽  
Voluntary Wheel

Migraine is a complex neurological disorder that affects three times more women than men and can be triggered by endogenous and exogenous factors. Stress is a common migraine trigger and exposure to early life stress increases the likelihood of developing chronic pain disorders later in life. Here, we used our neonatal maternal separation (NMS) model of early life stress to investigate whether female NMS mice have an increased susceptibility to evoked migraine-like behaviors and the potential therapeutic effect of voluntary wheel running. NMS was performed for 3 h/day during the first 3 weeks of life and initial observations were made at 12 weeks of age after voluntary wheel running (Exercise, -Ex) or sedentary behavior (-Sed) for 4 weeks. Mast cell degranulation rates were significantly higher in dura mater from NMS-Sed mice, compared to either naïve-Sed or NMS-Ex mice. Protease activated receptor 2 (PAR2) protein levels in the dura were significantly increased in NMS mice and a significant interaction of NMS and exercise was observed for transient receptor potential ankyrin 1 (TRPA1) protein levels in the dura. Behavioral assessments were performed on adult (>8 weeks of age) naïve and NMS mice that received free access to a running wheel beginning at 4 weeks of age. Facial grimace, paw mechanical withdrawal threshold, and light aversion were measured following direct application of inflammatory soup (IS) onto the dura or intraperitoneal (IP) nitroglycerin (NTG) injection. Dural IS resulted in a significant decrease in forepaw withdrawal threshold in all groups of mice, while exercise significantly increased grimace score across all groups. NTG significantly increased grimace score, particularly in exercised mice. A significant effect of NMS and a significant interaction effect of exercise and NMS were observed on hindpaw sensitivity following NTG injection. Significant light aversion was observed in NMS mice, regardless of exercise, following NTG. Finally, exercise significantly reduced calcitonin gene-related peptide (CGRP) protein level in the dura of NMS and naïve mice. Taken together, these findings suggest that while voluntary wheel running improved some measures in NMS mice that have been associated with increased migraine susceptibility, behavioral outcomes were not impacted or even worsened by exercise.

scholarly journals A Novel Mouse Model for Acute and Long-Lasting Consequences of Early Life Stress

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4892-4900 ◽  
Author(s):  
Courtney J. Rice ◽  
Curt A. Sandman ◽  
Mohammed R. Lenjavi ◽  
Tallie Z. Baram
Keyword(s):  
Mouse Model ◽  
Paraventricular Nucleus ◽  
Life Stress ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Early Life Stress ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Basal Plasma

Chronic early-life stress (ES) exerts profound acute and long-lasting effects on the hypothalamic-pituitary-adrenal system, with relevance to cognitive function and affective disorders. Our ability to determine the molecular mechanisms underlying these effects should benefit greatly from appropriate mouse models because these would enable use of powerful transgenic methods. Therefore, we have characterized a mouse model of chronic ES, which was provoked in mouse pups by abnormal, fragmented interactions with the dam. Dam-pup interaction was disrupted by limiting the nesting and bedding material in the cages, a manipulation that affected this parameter in a dose-dependent manner. At the end of their week-long rearing in the limited-nesting cages, mouse pups were stressed, as apparent from elevated basal plasma corticosterone levels. In addition, steady-state mRNA levels of CRH in the hypothalamic paraventricular nucleus of ES-experiencing pups were reduced, without significant change in mRNA levels of arginine vasopressin. Rearing mouse pups in this stress-provoking cage environment resulted in enduring effects: basal plasma corticosterone levels were still increased, and CRH mRNA levels in paraventricular nucleus remained reduced in adult ES mice, compared with those of controls. In addition, hippocampus-dependent learning and memory functions were impaired in 4- to 8-month-old ES mice. In summary, this novel, robust model of chronic early life stress in the mouse results in acute and enduring neuroendocrine and cognitive abnormalities. This model should facilitate the examination of the specific genes and molecules involved in the generation of this stress as well as in its consequences.

Abstract 335: Vascular Histone Deacetylase Mediates Early Life Stress-Induced Endothelial Dysfunction

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Dao H Ho ◽  
Jennifer S Pollock
Keyword(s):  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Histone Deacetylase ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Chromatin Modification ◽  
Early Life Stress ◽  
Mrna Levels

Chromatin remodeling is an important factor in the etiology of vascular pathologies. Also, early life stress (ELS) is linked to increased risk of vascular disease in adults. We used maternal separation with early weaning (MSEW) to study mechanisms of ELS-mediated adult vascular dysfunction in male C57BL/6J mice. Litters were subjected to maternal separation 4h/day (postnatal day (PD) 2-5) and 8h/day (PD6-16), and weaned at PD17. Control (CON) litters were undisturbed until weaning at PD21. Subsequent experiments were performed at 12 weeks old. MSEW blunted aortic ACh-mediated vasorelaxation (MSEW: 68% vs CON: 90%, p=0.01), while SNP-induced vasorelaxation was similar in CON and MSEW aortae. Apocynin (300 μM) and superoxide dismutase (100 U/mL) normalized MSEW-induced endothelial dysfunction. We hypothesize that ELS induces aortic endothelial dysfunction by increasing NADPH oxidase expression and/or decreasing nitric oxide synthase 3 (NOS3) expression. Aortic protein expression of NADPH oxidase subunit p67 was elevated in MSEW mice (45% increase from CON, n=11, p=0.02). NOS3 protein expression and NOS3 serine 1177 phosphorylation was not different between groups, indicating that NOS3 activation by phosphorylation does not contribute to ELS-induced endothelial dysfunction. We further hypothesize that chromatin modification mediates ELS-induced endothelial dysfunction. Aortic mRNA expressions of 84 chromatin modification enzymes (methyltransferases, demethylases, acetyltransferases, deacetylases) were assessed by qRT-PCR. Only histone deacetylase (HDAC) 1, 6 and 9 mRNA levels were significantly upregulated in MSEW aortae compared to CON (17%, 29% and 67% increase, respectively, p<0.05). However, only HDAC 9 protein expression was elevated in MSEW aortae (2 fold increase from CON, n=6, p=0.01). Accordingly, histone 3 lysine acetylation was slightly decreased in MSEW aortae (16% decrease from CON, n=6, p = 0.06). Pretreatment of aortae with an HDAC inhibitor, trichostatin A (TSA), normalized ACh-induced vasorelaxation in MSEW mice (MSEW: 68% vs MSEW + TSA: 88%, p=0.02), while not affecting ACh-induced vasorelaxation in CON mice. We conclude that ELS induces endothelial dysfunction, most likely, through an HDAC 9-mediated pathway.

The Role of Early Life Stress in HPA Axis and Anxiety

2020 ◽  
pp. 141-153 ◽  
Author(s):  
Mario F. Juruena ◽  
Filip Eror ◽  
Anthony J. Cleare ◽  
Allan H. Young
Keyword(s):  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

(267) The Influence of Long-Term Western Diet and Voluntary Exercise in an Early Life Stress Mouse Model of Co-Morbid Disorders

2019 ◽  
Vol 20 (4) ◽  
pp. S41
Author(s):  
O. Eller-Smith ◽  
X. Yang ◽  
E. Morris ◽  
J. Thyfault ◽  
J. Christianson
Keyword(s):  
Mouse Model ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Western Diet ◽  
Voluntary Exercise

scholarly journals Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

2020 ◽  
Vol 21 (19) ◽  
pp. 7212
Author(s):  
Mayumi Nishi
Keyword(s):  
Child Abuse ◽  
Hpa Axis ◽  
Brain Function ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Emotional Behavior ◽  
Neural Basis ◽  
The Brain

Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.

scholarly journals Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence

2011 ◽  
Vol 23 (4) ◽  
pp. 1039-1058 ◽  
Author(s):  
Marilyn J. Essex ◽  
Elizabeth A. Shirtcliff ◽  
Linnea R. Burk ◽  
Paula L. Ruttle ◽  
Marjorie H. Klein ◽  
...  
Keyword(s):  
Mental Health ◽  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Specific Activity ◽  
Early Life Stress ◽  
Hierarchical Linear Model ◽  
Mental Health Symptoms ◽  
Health Symptoms ◽  
Hypothalamic Pituitary Adrenal

AbstractThe hypothalamic–pituitary–adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

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