scholarly journals Modulation of the Hypothalamic Nutrient Sensing Pathways by Sex and Early-Life Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Silvie R. Ruigrok ◽  
Nina Stöberl ◽  
Kit-Yi Yam ◽  
Chiara de Lucia ◽  
Paul J. Lucassen ◽  
...  
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Life Stress ◽  
Early Life ◽  
Disease Risk ◽  
Energy State ◽  
Early Life Stress ◽  
Nutrient Sensing ◽  
Future Research ◽  
Expression Of Genes

There are sex differences in metabolic disease risk, and early-life stress (ES) increases the risk to develop such diseases, potentially in a sex-specific manner. It remains to be understood, however, how sex and ES affect such metabolic vulnerability. The hypothalamus regulates food intake and energy expenditure by sensing the organism’s energy state via metabolic hormones (leptin, insulin, ghrelin) and nutrients (glucose, fatty acids). Here, we investigated if and how sex and ES alter hypothalamic nutrient sensing short and long-term. ES was induced in mice by limiting the bedding and nesting material from postnatal day (P)2-P9, and the expression of genes critical for hypothalamic nutrient sensing were studied in male and female offspring, both at P9 and in adulthood (P180). At P9, we observed a sex difference in both Ppargc1a and Lepr expression, while the latter was also increased in ES-exposed animals relative to controls. In adulthood, we found sex differences in Acacb, Agrp, and Npy expression, whereas ES did not affect the expression of genes involved in hypothalamic nutrient sensing. Thus, we observe a pervasive sex difference in nutrient sensing pathways and a targeted modulation of this pathway by ES early in life. Future research is needed to address if the modulation of these pathways by sex and ES is involved in the differential vulnerability to metabolic diseases.

P.207 Sex differences in cocaine consumption vulnerability induced by early-life stress in mice

2021 ◽  
Vol 44 ◽  
pp. S20-S21
Author(s):  
A. Castro-Zavala ◽  
A. Martín-Sánchez ◽  
L. Montalvo-Martínez ◽  
A. Camacho-Morales ◽  
O. Valverde
Keyword(s):  
Sex Differences ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

scholarly journals Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation

2020 ◽  
Vol 10 (7) ◽  
pp. 447 ◽  
Author(s):  
Héctor González-Pardo ◽  
Jorge L. Arias ◽  
Eneritz Gómez-Lázaro ◽  
Isabel López Taboada ◽  
Nélida M. Conejo
Keyword(s):  
Sex Differences ◽  
Prefrontal Cortex ◽  
Mitochondrial Function ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Dopamine Turnover ◽  
Mitochondrial Energy Metabolism ◽  
Brain Mitochondrial Function

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-α and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.

P.579 Sex differences in depressive-like behavior in adult rats subjected to early life stress

2019 ◽  
Vol 29 ◽  
pp. S405
Author(s):  
N. Broshevitskaya ◽  
I. Pavlova ◽  
M. Zaichenko ◽  
V. Gruzdeva ◽  
G. Grigoryan
Keyword(s):  
Sex Differences ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Adult Rats

scholarly journals Exacerbated obesogenic response in female mice exposed to early life stress is linked to fat depot-specific upregulation of leptin protein expression

2020 ◽  
Vol 319 (5) ◽  
pp. E852-E862
Author(s):  
Jacqueline R. Leachman ◽  
Mathew D. Rea ◽  
Dianne M. Cohn ◽  
Xiu Xu ◽  
Yvonne N. Fondufe-Mittendorf ◽  
...  
Keyword(s):  
Protein Expression ◽  
Fat Mass ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Disease Risk ◽  
Early Life Stress ◽  
Female Mice ◽  
Fat Depot ◽  
Leptin Expression

Early life stress (ELS) is an independent risk factor for increased BMI and cardiometabolic disease risk later in life. We have previously shown that a mouse model of ELS, maternal separation and early weaning (MSEW), exacerbates high-fat diet (HF)-induced obesity only in adult female mice. Therefore, the aim of this study was to investigate 1) whether the short- and long-term effects of HF on leptin expression are influenced by MSEW in a sex-specific manner and 2) the potential epigenetic mechanisms underlying the MSEW-induced changes in leptin expression. After 1 wk of HF, both MSEW male and female mice displayed increased fat mass compared with controls ( P < 0.05). However, only MSEW female mice showed elevated leptin mRNA expression in gonadal white adipose tissue (gWAT; P < 0.05). After 12 wk of HF, fat mass remained increased only in female mice ( P < 0.05). Moreover, plasma leptin and both leptin mRNA and protein expression in gWAT were augmented in MSEW female mice compered to controls ( P < 0.05), but not in MSEW male mice. This association was not present in subcutaneous WAT. Furthermore, among 16 CpG sites in the leptin promoter, we identified three hypomethylated sites in tissue from HF-fed MSEW female mice compared with controls (3, 15, and 16, P < 0.05). These hypomethylated sites showed greater binding of key adipogenic factors such as PPARγ ( P < 0.05). Taken together, our study reveals that MSEW superimposed to HF increases leptin protein expression in a sex- and fat depot-specific fashion. Our data suggest that the mechanism by which MSEW increases leptin expression could be epigenetic.

scholarly journals Corticolimbic Circuit Structure Moderates an Association Between Early Life Stress and Later Trait Anxiety

2019 ◽  
Author(s):  
M. Justin Kim ◽  
Madeline J. Farber ◽  
Annchen R. Knodt ◽  
Ahmad R. Hariri
Keyword(s):  
Trait Anxiety ◽  
Life Stress ◽  
Early Life ◽  
Emotional Reactivity ◽  
Early Life Stress ◽  
Childhood Adversity ◽  
Structural Features ◽  
Individual Variability ◽  
Future Research ◽  
Wide Range

AbstractChildhood adversity is associated with a wide range of negative behavioral and neurodevelopmental consequences. However, individuals vary substantially in their sensitivity to such adversity. Here, we examined how individual variability in structural features of the corticolimbic circuit, which plays a key role in emotional reactivity, moderates the association between childhood adversity and later trait anxiety in 798 young adult university students. Consistent with prior research, higher self-reported childhood adversity was significantly associated with higher self-reported trait anxiety. However, this association was attenuated in participants with higher microstructural integrity of the uncinate fasciculus and greater thickness of the orbitofrontal cortex. These structural properties of the corticolimbic circuit may capture a neural profile of relative resiliency to early life stress, especially against the negative effects of childhood adversity on later trait anxiety. More generally, our findings highlight the potential utility in the simultaneous consideration of qualitatively different brain structural measures in explaining complex behavioral associations in future research.

scholarly journals Maternal Separation Induces Sex-Specific Differences in Sensitivity to Traumatic Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Dayan Knox ◽  
Stephanie A. Stout-Oswald ◽  
Melissa Tan ◽  
Sophie A. George ◽  
Israel Liberzon
Keyword(s):  
Risk Factors ◽  
Sex Differences ◽  
Animal Models ◽  
Traumatic Stress ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Male Rats

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with a high economic burden. Two risk factors for increasing the chances of developing PTSD are sex (being female) and early life stress. These risk factors suggest that early life stress-induced changes and sex differences in emotional circuits and neuroendocrinological systems lead to susceptibility to traumatic stress. Exploring mechanisms via which stress leads to specific effects can be accomplished in animal models, but reliable animal models that allow for an examination of how early life stress interacts with sex to increase susceptibility to traumatic stress is lacking. To address this, we examined the effects of early life stress [using the maternal separation (MS) model] and late adolescence/early adult traumatic stress [using the single prolonged stress (SPS) model] on startle reactivity, anxiety-like behavior in the open field (OF), and basal corticosterone levels in male and female rats. Female rats exposed to MS and SPS (MS/SPS) showed enhanced startle reactivity relative to MS/control female rats. Enhanced startle reactivity was not observed in MS/SPS male rats. Instead, non-maternally separated male rats that were exposed to SPS showed enhanced startle reactivity relative to controls. Female rats had enhanced locomotor activity in the OF and higher basal corticosterone levels in comparison to males, but measures in the OF and basal corticosterone were not affected by MS or SPS. Overall the results suggest that the combined MS and SPS models can be used to explore how changes in maternal care during infancy lead to sex differences in sensitivity to the effects of traumatic stress as adolescents and adults.

scholarly journals Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

2019 ◽  
Author(s):  
Alexandra B. Moussa-Tooks ◽  
Eric Larson ◽  
Alex F. Gimeno ◽  
Emma Leishman ◽  
Lisa A. Bartolomeo ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Cannabinoid Receptors ◽  
Early Life Stress ◽  
Future Research ◽  
Developmental Stress ◽  
Specific Effects ◽  
Effects Of Stress ◽  
Arachidonoyl Glycerol

AbstractStudies of early-life stress traditionally focus on glucocorticoid signaling as a modulator of neurodevelopmental risk, but emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling. Existing studies on stress-induced endocannabinoid dysregulation have focused on changes to cerebrum that are temporally proximal to stressors, but little is known about temporally distal effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Further, sex-specific effects of stress on cerebellar endocannabinoid tone are understudied. Following a naturalistic rodent model of early-life stress, limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids and related lipids and mRNA were assessed, and behavioral performance was evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar deep nuclei in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Transcriptomics for cerebellar interpositus nucleus revealed substantial sex effects, with minimal effects of stress. Stress did impair novel object recognition in both sexes and social preference in females. Taken together, the cerebellar endocannabinoids system exhibits robust sex-specific differences, malleable through early-life stress and perhaps also contributing to sexual differentiation of the brain. The current study may foster future research into stress as a risk factor for cerebellar-related dysfunctions.

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